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Fulltext Cytotoxicity, regulation of apoptotic and anti-apoptotic gene expression by IL-27 in MCF-7 and MDA-MB-231 breast cancer cell lines

Yap Wei Boon, Shaktypreya Nadarajah, Nadiah Shidik, Noorjahan Banu Mohammed Alitheen

Jurnal Sains Kesihatan Malaysia, 2018;16(101):15-22.
MyJurnal

Breast cancer is one of the commonest cancers among women. Conventional therapies cause adverse side effects in patients. Cytokine immunotherapy such as interleukin-27 (IL-27) has been sought as an alternative cancer treatment in recent years. IL-27 has been shown to improve anticancer immunity and anti-angiogenesis in cancers, however, its effect on apoptotic and anti-apoptotic gene expression especially in breast cancers is yet to be explored. Cytotoxicity of IL-27 in non-cancerous (184b5) and cancerous (MCF-7 and MDA-MB-231) breast cell lines was first determined for 24-72 h in this study. The results indicated that IL-27 treatment did not retard 184b5 cell growth, however, did inhibit MCF-7 (48 h) and MDA-MB-231 (72 h) cell growth with IC50 at 442 and 457 ng/ml, respectively. Apoptotic (TRAIL, FADD, FAS, caspase-3 and caspase-8) and anti-apoptotic (BCL-2, AKT, and COX-2) genes were then amplified from untreated (control) and treated breast cancer cells and studied. TRAIL, caspase-3, caspase-8 gene expression was significantly (p < 0.05) upregulated in treated MCF-7 (442 ng/ml) and MDA-MB-231 (457 ng/ml) cells. Expression of FADD and FAS genes was not detected in both control and treated MCF-7 and MDA-MB-231 cells. COX-2 gene was also not expressed by MCF-7 cells, but reduced significantly (p < 0.05) in treated MDA-MB-231 cells. In MDA-MB-231 cells, IL-27 treatment seemed to slightly enhance the expression of AKT and BCL-2 genes which, on the other hand, was downregulated in treated MCF-7 cells. Conclusively, IL-27 is able to inhibit breast cancer cell growth and regulate apoptotic and anti-apoptotic gene expression in breast cancer cells.

Matched MeSH terms: Interleukins
Raised levels of Il-6, Il-17a, and Il-22 in fatal leptospirosis

Wan Yusoff WSY, Abdullah M, Sekawi Z, Amran F, Yuhana MY, Mohd Taib N, et al.

Eur J Clin Microbiol Infect Dis, 2019 Dec;38(12):2349-2353.
PMID: 31529307 DOI: 10.1007/s10096-019-03699-5

Clinical manifestations of leptospirosis range from mild, common cold-like illness, to a life-threatening condition. The host immune response has been hypothesized to play a major role in leptospirosis outcome. Increased levels of inflammatory mediators, such as cytokines, may promote tissue damage that lead to increased disease severity. The question is whether cytokines levels may predict the outcome of leptospirosis and guide patient management. This study aimed to assess the association between Th1-, Th2-, and Th17-related cytokines with the clinical outcome of patients with leptospirosis. Different cytokine levels were measured in fifty-two plasma samples of hospitalized patients diagnosed with leptospirosis in Malaysia (January 2016-December 2017). Patients were divided into two separate categories: survived (n = 40) and fatal outcome (n = 12). Nineteen plasma samples from healthy individuals were obtained as controls. Cytokine quantification was performed using Simple Plex™ assays from ProteinSimple (San Jose, CA, USA). Measurements were done in triplicate and statistical analysis was performed using GraphPad software and SPSS v20. IL-6 (p = 0.033), IL-17A (p = 0.022), and IL-22 (p = 0.046) were significantly elevated in fatal cases. IL-17A concentration (OR 1.115; 95% CI 1.010-1.231) appeared to be an independent predictor of fatality of leptospirosis. Significantly higher levels of TNF-α (p ≤ 0.0001), IL-6 (p ≤ 0.0001), IL-10 (p ≤ 0.0001), IL-12 (p ≤ 0.0001), IL17A (p ≤ 0.0001), and IL-18 (p ≤ 0.0001) were observed among leptospirosis patients in comparison with healthy controls. Our study shows that certain cytokine levels may serve as possible prognostic biomarkers in leptospirosis patients.

Matched MeSH terms: Interleukins/blood
Fulltext Clinical and genetic differences between pustular psoriasis subtypes

Twelves S, Mostafa A, Dand N, Burri E, Farkas K, Wilson R, et al.

J Allergy Clin Immunol, 2019 03;143(3):1021-1026.
PMID: 30036598 DOI: 10.1016/j.jaci.2018.06.038

BACKGROUND: The term pustular psoriasis indicates a group of severe skin disorders characterized by eruptions of neutrophil-filled pustules. The disease, which often manifests with concurrent psoriasis vulgaris, can have an acute systemic (generalized pustular psoriasis [GPP]) or chronic localized (palmoplantar pustulosis [PPP] and acrodermatitis continua of Hallopeau [ACH]) presentation. Although mutations have been uncovered in IL36RN and AP1S3, the rarity of the disease has hindered the study of genotype-phenotype correlations.
OBJECTIVE: We sought to characterize the clinical and genetic features of pustular psoriasis through the analysis of an extended patient cohort.
METHODS: We ascertained a data set of unprecedented size, including 863 unrelated patients (251 with GPP, 560 with PPP, 28 with ACH, and 24 with multiple diagnoses). We undertook mutation screening in 473 cases.
RESULTS: Psoriasis vulgaris concurrence was lowest in PPP (15.8% vs 54.4% in GPP and 46.2% in ACH, P

Matched MeSH terms: Interleukins/genetics
Fulltext Association between IL-31 serum levels and other predisposing factors with allergic diseases in HRPZ II and HUSM, Kelantan, Malaysia

Siti Noor Syuhada Muhammad Amin, Noor Suryani Mohd Ashari, Wan Zuraida Wan Abd. Hamid, Azriani Ab Rahman, Azman Azid

Malaysian Journal of Public Health Medicine, 2017;17(2):66-73.

Interleukin 31 (IL-31)is one of the cytokines which appears to be an important regulator of Th2 responses. Previous study has been done to determine IL-31 serums levels in atopic dermatitis (AD). However, the serum levels of IL-31 in allergic rhinitis (AR) and atopic asthma (AA) is not many reported and still unclear. The objective of this cross sectional study is to determine an association between IL-31 and other predisposing factors with allergic diseases in HRPZ II (Hospital Raja PerempuanZainab II) and HUSM (Hospital UniversitiSains), Kelantan, Malaysia. This study involved 70 patients of AD, 70 patients of AR, 70 patients of AA and 70 healthy controls from staffs and people in HUSM.Five milliliters of blood were withdrawn and centrifuged for 5 minutes at 2000 rpm to obtain the serum and analyzed for IL-31 levels by using enzymelinked immunosorbent (ELISA) kits (Human IL 31 Duoset, R&D System). Simple and multiple logistic regressions were used to analyze the association between IL-31 levels and predisposing factors among allergic diseases. The levels of IL-31 and other predisposing factors showed significant associations in smoking status, occupational exposure and area of living for AD and AR, however in AA, the significant association only found in smoking status and occupational exposure. In conclusion, we found that there were associations between IL-31 serum levels and other predisposing factors with AD, AR and AA. The findings can be the pilot study to determine IL-31 levels in allergic diseases in Malaysia.

Matched MeSH terms: Interleukins
Palm tocotrienols inhibit proliferation of murine mammary cancer cells and induce expression of interleukin-24 mRNA

Selvaduray KR, Radhakrishnan AK, Kutty MK, Nesaretnam K

J Interferon Cytokine Res, 2010 Dec;30(12):909-16.
PMID: 21121862 DOI: 10.1089/jir.2010.0021

Several mechanisms have been postulated for the anticancer effects of tocotrienols. In this study, for the first time, the anticancer effect of tocotrienols is linked to increased expression of interleukin-24 (IL-24) mRNA, a cytokine reported to have antitumor effects in many cancer models. Tocotrienol isomers (α-T3, γ-T3, and δ-T3) and tocotrienol-rich fraction (TRF) inhibited the growth of the 4T1 murine mammary cancer cells (P γ-T3 > TRF > α-T3 > α-T, which was similar to their antiproliferative effects. The IL-24 mRNA levels in tumor tissues of BALB/c mice supplemented with TRF increased 2-fold when compared with control mice. Increased levels of IL-24 have been associated with inhibition of tumor growth and angiogenesis. Treatment of 4T1 cells with TRF and δ-T3 significantly decreased IL-8 and vascular endothelial growth factor mRNA levels. Hence, we report that tocotrienols have potent antiangiogenic and antitumor effects that is associated with increased levels of IL-24 mRNA.

Matched MeSH terms: Interleukins/genetics*; Interleukins/immunology
Targeting interleukins in chronic airway diseases using advanced drug delivery

Satija S, Mehta M, Gupta G, Chellappan DK, Dua K

Future Med Chem, 2020 10;12(20):1805-1807.
PMID: 33016120 DOI: 10.4155/fmc-2020-0190
Matched MeSH terms: Interleukins/antagonists & inhibitors*; Interleukins/metabolism
Inhibitory effect of selected medicinal plants on the release of pro-inflammatory cytokines in lipopolysaccharide-stimulated human peripheral blood mononuclear cells

Salim E, Kumolosasi E, Jantan I

J Nat Med, 2014 Jul;68(3):647-53.
PMID: 24799081 DOI: 10.1007/s11418-014-0841-0

The inhibitory activities of the methanol extracts from 20 selected medicinal plants on the release of pro-inflammatory cytokines in human peripheral blood mononuclear cells (PBMCs) were evaluated. The major compound from the most active plant extract was also investigated. The inhibitory effect of the methanol extracts on the release of pro-inflammatory cytokines was tested by incubating PBMCs with the sample and then stimulating by lipopolysaccharide at 0.1 μg/ml. The level of cytokines was determined using enzyme-linked immunosorbent assay. Among the extracts tested, Andrographis paniculata extract demonstrated the strongest inhibition of interleukin (IL)-1β, IL-1α, and IL-6 release, with IC50 values of 1.54, 1.06, and 0.74 μg/ml, respectively. The IC50 value of A. paniculata extract was significantly higher than that of andrographolide on IL-1α, IL-1β, and IL-6 (p

Matched MeSH terms: Interleukins/metabolism
D-pinitol mitigates tumor growth by modulating interleukins and hormones and induces apoptosis in rat breast carcinogenesis through inhibition of NF-κB

Rengarajan T, Nandakumar N, Rajendran P, Ganesh MK, Balasubramanian MP, Nishigaki I

J Physiol Biochem, 2015 Jun;71(2):191-204.
PMID: 25827943 DOI: 10.1007/s13105-015-0397-9

Breast cancer is the most prevalent malignant neoplasm in the world, and chemoprevention through dietary intervention strategy is an emerging option to reduce the incidence. D-pinitol (DP), a major component of soya bean, possesses attractive biological actions. We have investigated whether D-pinitol have an effect on tumor growth in vivo against 7,12-dimethylbenz(a)anthracene (DMBA)-initiated rat mammary carcinogenesis and investigated its mechanism of action. Tumors were induced in Sprague-Dawley (SD) rats by a gastric dose of 20 mg/kg DMBA, and after 13 weeks of induction period, the rats were orally administered with D-pinitol for 45 days. At the end of the assay, animals in carcinogen control group prompted a tumor incidence of 100 % and developed a tumor volume of 8.35 ± 0.56, which was significantly reduced to 5.74 ± 0.32 for the animals treated with D-pinitol. The D-pinitol treatment not only decreased the tumor volume but also further examination revealed that tumors from animals that received D-pinitol reduced nuclear factor kappa B (NF-κB) activation which in turn results in modulation of its downstreaming p53 and proteins of caspase-3 family. Bcl-2 expression and caspase-3 activation were also decreased after D-pinitol supplementation leading to induction of apoptosis and finally cell death. Furthermore, the status of the inflammatory cytokines such as tumor necrosis factor-α (TNF-α), interleukin (IL)-2, IL-6, and tumor markers, lipid profile, and hormones was also significantly declined up on D-pinitol administration. Thus, it reveals the collective involvement of the above-mentioned parameters along with NF-κB signaling through which D-pinitol induces apoptosis and subsequently suppresses breast cancer during DMBA-induced rat breast carcinogenesis.

Matched MeSH terms: Interleukins/metabolism*
Fulltext Blastocystis sp. in Irritable Bowel Syndrome (IBS)--Detection in Stool Aspirates during Colonoscopy

Ragavan ND, Kumar S, Chye TT, Mahadeva S, Shiaw-Hooi H

PLoS One, 2015;10(9):e0121173.
PMID: 26375823 DOI: 10.1371/journal.pone.0121173

Blastocystis is one of the most common gut parasites found in the intestinal tract of humans and animals. Its' association with IBS is controversial, possibly as a result of irregular shedding of parasites in stool and variation in stool detection. We aimed to screen for Blastocystis in colonic stool aspirate samples in adult patients with and without IBS undergoing colonoscopy for various indications and measure the interleukin levels (IL-8, IL-3 and IL-5). In addition to standard stool culture techniques, polymerase chain reaction (PCR) techniques were employed to detect and subtype Blastocystis. All the serum samples collected were subjected for ELISA studies to measure the interleukin levels (IL-8, IL-3 and IL-5). Among 109 (IBS n = 35 and non-IBS n = 74) adults, direct stool examination and culture of colonic aspirates were initially negative for Blastocystis. However, PCR analysis detected Blastocystis in 6 (17%) IBS and 4 (5.5%) non-IBS patients. In the six positive IBS patients by PCR method, subtype 3 was shown to be the most predominant (3/6: 50%) followed by subtype 4 (2/6; 33.3%) and subtype 5 (1/6; 16.6%). IL-8 levels were significantly elevated in the IBS Blasto group and IBS group (p<0.05) compared to non-IBS and non-IBS Blasto group. The level of IL-3 in were seen to be significantly higher in than IBS Blasto group and IBS group (p<0.05) compared to non-IBS. Meanwhile, the IL-5 levels were significantly higher in IBS Blasto group (p<0.05) compared to non-IBS and non-IBS Blasto group. This study implicates that detecting Blastosystis by PCR method using colonic aspirate samples during colonoscopy, suggests that this may be a better method for sample collection due to the parasite's irregular shedding in Blastocystis-infected stools. Patients with IBS infected with parasite showed an increase in the interleukin levels demonstrate that Blastocystis does have an effect in the immune system.

Matched MeSH terms: Interleukins/blood
Fulltext Gallic acid attenuates dextran sulfate sodium-induced experimental colitis in BALB/c mice

Pandurangan AK, Mohebali N, Norhaizan ME, Looi CY

Drug Des Devel Ther, 2015;9:3923-34.
PMID: 26251571 DOI: 10.2147/DDDT.S86345

Gallic acid (GA) is a polyhydroxy phenolic compound that has been detected in various natural products, such as green tea, strawberries, grapes, bananas, and many other fruits. In inflammatory bowel disease, inflammation is promoted by oxidative stress. GA is a strong antioxidant; thus, we evaluated the cytoprotective and anti-inflammatory role of GA in a dextran sulfate sodium (DSS)-induced mouse colitis model. Experimental acute colitis was induced in male BALB/c mice by administering 2.5% DSS in the drinking water for 7 days. The disease activity index; colon weight/length ratio; histopathological analysis; mRNA expressions of IL-21 and IL-23; and protein expression of nuclear erythroid 2-related factor 2 (Nrf2) were compared between the control and experimental mice. The colonic content of malondialdehyde and the activities of superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase activity were examined as parameters of the redox state. We determined that GA significantly attenuated the disease activity index and colon shortening, and reduced the histopathological evidence of injury. GA also significantly (P<0.05) reduced the expressions of IL-21 and IL-23. Furthermore, GA activates/upregulates the expression of Nrf2 and its downstream targets, including UDP-GT and NQO1, in DSS-induced mice. The findings of this study demonstrate the protective effect of GA on experimental colitis, which is probably due to an antioxidant nature of GA.

Matched MeSH terms: Interleukins/genetics; Interleukins/metabolism
Modelling the immunopathophysiology of Brucella melitensis and its lipopolysaccharide in mice infected via oral route of exposure

Osman AY, Kadir AA, Jesse FF, Saharee AA

Microb Pathog, 2019 Nov;136:103669.
PMID: 31445124 DOI: 10.1016/j.micpath.2019.103669

Brucella melitensis is one of the leading zoonotic pathogens with significant economic implications in animal industry worldwide. Lipopolysaccharide, however, remains by far the major virulence with substantial role in diseases pathogenesis. Nonetheless, the effect of B. melitensis and its lipopolysaccharide on immunopathophysiological aspects largely remains an enigma. This study examines the effect of B.melitensis and its lipopolysaccharide on immunopathophysiological parameters following experimental infection using mouse model. Eighty four (n = 84) mice, BALB/c, both sexes with equal gender distribution and 6-8 weeks-old were randomly assigned into three groups. Group 1-2 (n = 72) were orally inoculated with 0.4 mL containing 109 CFU/mL of B. melitensis and its LPS, respectively. Group 3 (n = 12) was challenged orally with phosphate buffered saline and served as a control group. Animals were observed for clinical signs, haematological and histopathological analysis for a period of 24 days post-infection. We hereby report that B.melitensis infected group demonstrated significant clinical signs and histopathological changes than LPS infected group. However, both infected groups showed elevated levels of interleukins (IL-1β and IL-6) and antibody levels (IgM and IgG) with varying degrees of predominance in LPS infected group than B. melitensis infected group. For hormone analysis, low levels of progesterone, estradiol and testosterone were observed in both B. melitensis and LPS groups throughout the study period. Moreover, in B. melitensis infected group, the organism was re-isolated from the organs and tissues of gastrointestinal, respiratory and reproductive systems thereby confirming the infection and transmission dynamics. This report is the first detailed investigation comparing the infection progression and host responses in relation to the immunopathophysiological aspects in a mouse model after oral inoculation with B. melitensis and its lipopolysaccharide.

Matched MeSH terms: Interleukins/blood
Immuno-pathophysiological responses of mouse model to experimental infection with Brucella melitensis and its lipopolysaccharides via intraperitoneal route

Osman AY, Abdullah FF, Kadir AA, Saharee AA

Microb Pathog, 2016 Nov;100:17-29.
PMID: 27591112 DOI: 10.1016/j.micpath.2016.08.019

Brucella melitensis is one of the major zoonotic pathogens with significant economic implications worldwide. The pathogenicity is complex and not always well understood. Lipopolysaccharide (LPS) remains the major virulent factor of B. melitensis and responsible for the mechanism by which the pathogen causes its deleterious effects. In this study, 84 mice of 6-8 weeks old of both sexes were divided equally into 3 groups; namely Brucella melitensis infected group, lipopolysaccharide (LPS) infected group and control group. The former two groups contained 36 mice each with equal gender distribution. The control group consisted of 12 mice only. Animals in B. melitensis infected group, a single inoculum of 0.4 ml containing 10(9) of B. melitensis were intraperitoneally challenged while animals in LPS group, a single dose of 0.4 ml containing LPS extracted from the B. melitensis were intraperitoneally inoculated. Animals in control group received intraperitoneally, a single dose of 0.4 ml phosphate buffered saline (PBS) of pH7. Animals that were infected intraperitoneally with B. melitensis demonstrated significant clinical presentation; gross and histo-pathological evidence than LPS infected group. However, both infected groups showed elevated levels of interleukins (IL-1β and IL6), antibody levels (IgM an IgG) as early as 3 days post-infection with predominance in LPS infected group. In contrast, low levels of sex related hormonal changes in which LPS infected group showed the least concentration were also detected throughout the experimental period. In conclusion, B. melitensis can be transmitted via gastrointestinal, respiratory and reproductive tract. Moreover, LPS stimulated significantly the innate and acquired immune system without significant systemic dysfunction, suggesting potentiality of the protective properties of this component as alternative vaccine for brucellosis infection.

Matched MeSH terms: Interleukins/blood
Fulltext Association between genetic polymorphisms and external apical root resorption: A systematic review and meta-analysis

Nowrin SA, Jaafar S, Ab Rahman N, Basri R, Alam MK, Shahid F

Korean J Orthod, 2018 Nov;48(6):395-404.
PMID: 30450332 DOI: 10.4041/kjod.2018.48.6.395

Objective: To date, only a few studies have investigated the relationships between genetic polymorphisms and external apical root resorption (EARR). Hence, the aim of this systematic review was to explore the relationship between different gene polymorphisms and their association with EARR.
Methods: A complete literature search was conducted by two independent reviewers. The PubMed, Science Direct, and Scopus databases were searched. In addition, the bibliographies of all textbooks and relevant articles were searched manually. A meta-analysis was performed using data entered into the electronic databases until February 28, 2017.
Results: On the basis of the search, we identified 17 and 7 publications for the systematic review and meta-analysis, respectively. Odds ratio (OR) was used to evaluate the association of the interleukin 1B (+3954) polymorphism and the risk of EARR. The overall OR from the studies was used to estimate the risk of EARR. However, no association was found and no publication bias was apparent for the risk of EARR in patients receiving orthodontic treatment.
Conclusions: More research on the relationship between gene polymorphism and EARR is necessary to determine better specificity of possible interactions.

Matched MeSH terms: Interleukins
Antioxidant, anti-inflammatory and synergistic anti-hyperglycemic effects of Malaysian propolis and metformin in streptozotocin-induced diabetic rats

Nna VU, Abu Bakar AB, Md Lazin MRML, Mohamed M

Food Chem Toxicol, 2018 Oct;120:305-320.
PMID: 30026088 DOI: 10.1016/j.fct.2018.07.028

Diabetes mellitus is characterized by hyperglycemia which causes oxidative stress. Propolis has been reported to have antihyperglycemic and antioxidant potentials. The present study therefore examined the anti-hyperglycemic, antioxidant and anti-inflammatory activities of Malaysian propolis (MP) using streptozotocin-induced diabetic rats. Ethanol extract of MP showed in vitro antioxidant (DPPH, FRAP and H2O2 radical scavenging) and α-glucosidase inhibition activities. Male Sprague Dawley rats were either treated with distilled water (normal control and diabetic control), MP (300 mg/kg b. w.), metformin (Met) (300 mg/kg b. w.) or both. After four weeks, fasting blood glucose decreased, while body weight change and serum insulin level increased significantly in MP, Met and MP + Met treated diabetic groups compared to diabetic control (DC) group. Furthermore, pancreatic antioxidant enzymes, total antioxidant capacity, interleukin (IL)-10 and proliferating cell nuclear antigen increased, while malondialdehyde, nuclear factor-kappa B (p65), tumor necrosis factor alpha, IL-1β and cleaved caspase-3 decreased significantly in the treated diabetic groups compared to DC group. Histopathology of the pancreas showed increased islet area and number of beta cells in the treated groups, compared to DC group, with D + MP + Met group comparable to normal control. We conclude that MP has anti-hyperglycemic, antioxidant, anti-inflammatory and antiapoptotic potentials, and exhibits synergistic effect with metformin.

Matched MeSH terms: Interleukins
Fulltext Peptide regulatory factors. Intercellular signalling molecules regulating tissue (re) modelling

Ng KW

Med J Malaysia, 1992 Mar;47(1):3-10.
PMID: 1387446
Matched MeSH terms: Interleukins/physiology
Fulltext CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

Mohd Shukri ND, Farah Izati A, Wan Ghazali WS, Che Hussin CM, Wong KK

Front Immunol, 2021;12:675250.
PMID: 34149710 DOI: 10.3389/fimmu.2021.675250

The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.

Matched MeSH terms: Interleukins/blood; Interleukins/metabolism
IL36RN mutations define a severe autoinflammatory phenotype of generalized pustular psoriasis

Hussain S, Berki DM, Choon SE, Burden AD, Allen MH, Arostegui JI, et al.

J Allergy Clin Immunol, 2015 Apr;135(4):1067-1070.e9.
PMID: 25458002 DOI: 10.1016/j.jaci.2014.09.043
Matched MeSH terms: Interleukins/genetics*
Local and Systemic Expression Profile of IL-10, IL-17, IL-27, IL-35, and IL-37 in Periodontal Diseases: A Cross-sectional Study

Ho JY, Yeo BS, Yang XL, Thirugnanam T, Hakeem MF, Sahu PS, et al.

J Contemp Dent Pract, 2021 Jan 01;22(1):73-79.
PMID: 34002713

AIM: This study aimed to compare the level of interleukin (IL)-10, IL-17, IL-27, IL-35, and IL-37 in the gingival crevicular fluid (GCF) and human plasma of subjects with periodontal disease.
MATERIALS AND METHODS: In this cross-sectional study conducted over a 3-month period at a primary dental clinic in Malaysia, 45 participants were recruited via consecutive sampling and assigned into three groups, namely healthy periodontium group (n = 15), gingivitis group (n = 15), and periodontitis group (n = 15). Gingival crevicular fluid and plasma samples were collected from each participant. Enzyme-linked immunosorbent assay test was conducted to measure the concentration of IL-10, IL-17, IL-27, IL-35, and IL-37. Kruskal-Wallis H test was used to compare the interleukin levels between patient groups.
RESULTS: In GCF samples, IL-17 level was the highest in the periodontitis group (p <0.05), while IL-27 was the lowest (p <0.05). Meanwhile, plasma levels of IL-27 and IL-37 were significantly lower (p <0.05) in the periodontitis group, but plasma IL-35 levels were observed to rise with increasing disease severity.
CONCLUSION: There are reduced local and systemic levels of IL-27 in periodontitis patients.
CLINICAL SIGNIFICANCE: Periodontal diseases exert both local and systemic effects, resulting in the destruction of the tooth-supporting structures and contributing to the systemic inflammatory burden. Some of the cytokines that were investigated in the current study, IL-17, IL-27, IL-35, and IL-37, can be potential biomarkers that warrant further longitudinal clinical studies to determine their usefulness as prognostic/diagnostic markers.

Matched MeSH terms: Interleukins/analysis
IFN-γ and IL-18 in conditioned media of parasite-infected host and IL-21-silenced colorectal cancer cells

Ge P, Ong CY, Abdalkareem AE, Khoo BY, Yuan B

Exp Ther Med, 2021 Feb;21(2):103.
PMID: 33335566 DOI: 10.3892/etm.2020.9535

The presence of certain soluble factors may provide a possible selective advantage for a parasite to gradually modify cell proliferation in neighbouring cells, which may result in chronic diseases. These soluble factors present in the conditioned medium also allow the parasite to invade rapidly into more host cells. The present study aimed to determine the levels of a group of type 1 T helper (Th1) cytokines in the conditioned media of host cells infected with parasites and in IL-21-silenced colorectal cancer cells. The conditioned media of human foreskin fibroblasts (HFFs) parasitized with the RH and ME49 strains of Toxoplasma gondii for 10 days were prepared, and subsequently the levels of the Th1 cytokines in the conditioned media were determined by ELISA. HFFs were incubated with the growth media containing selected soluble factors, and cell proliferation markers were subsequently analysed by reverse transcription-quantitative PCR. The mRNA expression level of cell proliferation markers was also examined in IL-21-silenced HCT116 cells, where the levels of soluble factors in the conditioned media were also determined as aforementioned. The results of the present study demonstrated that HFFs parasitized with ME49 released elevated levels of IFN-γ and lower levels of IL-18 into the conditioned medium compared with the controls. These phenomena were not observed in the conditioned medium of HFFs parasitized with RH. Similar levels of these soluble factors were also detected in the conditioned medium of IL-21-silenced HCT116 cells. The results of the present study also revealed that Ki67 and proliferating cell nuclear antigen mRNA expression was altered in host cells incubated with various levels of IFN-γ and IL-18, as well as in IL-21-silenced HCT116 cells compared with the respective controls. In conclusion, the current study provided preliminary evidence on the fundamental molecular mechanisms of host-parasite interactions that result in chronic diseases, which may aid in the treatment of these diseases in the relevant endemic regions.

Matched MeSH terms: Interleukins
Fulltext Interleukin-27 exhibited anti-inflammatory activity during Plasmodium berghei infection in mice

Fazalul Rahiman SS, Basir R, Talib H, Tie TH, Chuah YK, Jabbarzare M, et al.

Trop Biomed, 2013 Dec;30(4):663-80.
PMID: 24522137 MyJurnal

Interleukin-27 (IL-27) has a pleiotropic role either as a pro-inflammatory or anti-inflammatory cytokine in inflammatory related diseases. The role and involvement of IL-27 during malaria was investigated and the effects of modulating its release on the production of major inflammatory cytokines and the histopathological consequences in major affected organs during the infection were evaluated. Results showed that IL-27 concentration was significantly elevated throughout the infection but no positive correlation with the parasitaemia development observed. Augmentation of IL-27 significantly elevated the release of anti-inflammatory cytokine, IL-10 whereas antagonising and neutralising IL-27 produced the opposite. A significant elevation of pro-inflammatory cytokines (IFN-γ and IL-6) was also observed, both during augmentation and inhibition of IL-27. Thus, it is suggested that IL-27 exerts an anti-inflammatory activity in the Th1 type response by signalling the production of IL-10 during malaria. Histopathological examination showed sequestration of PRBC in the microvasculature of major organs in malarial mice. Other significant histopathological changes include hyperplasia and hypertrophy of the Kupffer cells in the liver, hyaline membrane formation in lung tissue, enlargement of the white and red pulp followed by the disappearance of germinal centre of the spleen, and tubular vacuolation of the kidney tissues. In conclusion, it is suggested that IL-27 may possibly acts as an anti-inflammatory cytokine during the infection. Modulation of its release produced a positive impact on inflammatory cytokine production during the infection, suggesting its potential in malaria immunotherapy, in which the host may benefit from its inhibition.

Matched MeSH terms: Interleukins/blood; Interleukins/immunology*

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