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  1. Mei TTY, Aung HH, Tung WS, Naing C
    BMC Cancer, 2023 Sep 08;23(1):842.
    PMID: 37684564 DOI: 10.1186/s12885-023-11323-1
    BACKGROUND: The carcinogenesis of hepatocellular carcinoma is complicated, and genetic factor may have the role in the malignant transformation of liver cells. IL-10 gene polymorphisms have been investigated for their potential roles in hepatocellular carcinoma This study aimed to investigate the relationship between polymorphisms of IL-10 (-1082 A/G, -819 T/C, -592 A/C), and hepatocellular carcinoma by performing a meta-analysis with eligible individual studies.

    METHODS: This study followed the PRISMA 2020 Checklist. Relevant studies were searched in health-related databases. The Newcastle-Ottawa Scale criteria were used to evaluate the studies quality. Pooled odds ratio (OR) and its 95% confidence interval (CI) were used to determine the strength of association between each polymorphism and hepatocellular carcinoma using five genetic models. Stratification was done by ethnic groups. Trial sequential analysis (TSA) was performed to determine the required information size.

    RESULTS: Fifteen case-control studies (n = 8182) were identified. Overall, the heterozygous model showed a marginal significant association only between IL-10 (-1082 A/G) and hepatocellular carcinoma risk (OR: 0.82, 95% CI: 0.67-1.00, 9 studies). On stratification, IL-10 (-1082 A/G) was significantly associated with hepatocellular carcinoma risk in the non-Asian population under dominant (OR: 0.62, 95% CI: 0.45-0.86, 4 studies), heterozygous (OR: 0.60, 95% CI: 0.43-0.85) and allelic models (OR: 0.79, 95% CI: 0.64-0.99). IL-10 (-819 T/C) was significantly associated with hepatocellular carcinoma risk only among non-Asians under the dominant (OR: 1.47, 95% CI: 1.02-2.13, 8 studies), recessive (OR: 1.99, 95% CI: 1.03-3.86, and homozygous models (OR: 2.18, 95% CI: 1.13-4.23). For IL-10 (-592 A/C) with 11 studies, there was no significant association with hepatocellular carcinoma in all five genetic models (P values > 0.5). TSA plots indicated that the information size for firm evidence of effect was sufficient only for the analysis of IL-10 (-592 A/C), but not for the - 1082 A/G or -819 T/C.

    CONCLUSIONS: Findings suggest that IL-10 (-1082 A/G and - 819 T/C) polymorphisms are associated with hepatocellular carcinoma in ethnic-specific manner. However, this evidence is not conclusive because the sample size was insufficient. IL-10 (-592 A/C) polymorphism was not associated with hepatocellular carcinoma albeit with sufficient information size. Future well-designed large case-control studies on IL-10 (-1082 A/G and - 819 T/C) with different ethnicities are recommended.

    Matched MeSH terms: Interleukin-10/genetics
  2. Dooley NL, Chabikwa TG, Pava Z, Loughland JR, Hamelink J, Berry K, et al.
    Nat Commun, 2023 Nov 15;14(1):7387.
    PMID: 37968278 DOI: 10.1038/s41467-023-43181-7
    Plasmodium falciparum malaria drives immunoregulatory responses across multiple cell subsets, which protects from immunopathogenesis, but also hampers the development of effective anti-parasitic immunity. Understanding malaria induced tolerogenic responses in specific cell subsets may inform development of strategies to boost protective immunity during drug treatment and vaccination. Here, we analyse the immune landscape with single cell RNA sequencing during P. falciparum malaria. We identify cell type specific responses in sub-clustered major immune cell types. Malaria is associated with an increase in immunosuppressive monocytes, alongside NK and γδ T cells which up-regulate tolerogenic markers. IL-10-producing Tr1 CD4 T cells and IL-10-producing regulatory B cells are also induced. Type I interferon responses are identified across all cell types, suggesting Type I interferon signalling may be linked to induction of immunoregulatory networks during malaria. These findings provide insights into cell-specific and shared immunoregulatory changes during malaria and provide a data resource for further analysis.
    Matched MeSH terms: Interleukin-10/genetics
  3. Montazeri S, Nalliah S, Radhakrishnan AK
    Hereditas, 2010 Apr;147(2):94-102.
    PMID: 20536548 DOI: 10.1111/j.1601-5223.2009.02134.x
    Gestational diabetes mellitus (GDM), defined as carbohydrate intolerance diagnosed for the first time during pregnancy, affects both maternal and fetal health. Possession of a specific genetic polymorphism can be a predisposing factor for susceptibility to some diseases. The aim of this study was to investigate the association between single nucleotide polymorphisms (SNP) in the promoter gene of interleukin-10 (IL-10) as well as tumor necrosis factor-alpha (TNF alpha) with the development of GDM. Two hundred and twelve consecutive series of eligible normal pregnant women (controls) and gestational diabetes mellitus women were selected based on the study's inclusion and exclusion criteria. DNA was extracted from blood and genotyped for IL-10 at three positions and TNF alpha for gene polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Plasma levels of IL-10 and TNF alpha at different gestational periods as well as postpartum were quantified using enzyme linked immunosorbent assay (ELISA). The results of the study showed that the difference in the frequency of SNP at position -597 in the promoter of the human IL-10 gene between the control and GDM groups was statistically significant (p < 0.05). In contrast, there was no significant difference in the frequency of SNP at the other two sites in the promoter region of the human IL-10 gene (-824 and -1082) as well as position -308 in the promoter of the human TNF-alpha (p > 0.05). In addition, there was no significant difference between the two groups in terms of plasma levels of IL-10 as well as TNF alpha in different stages of pregnancy. SNP at position -597 was significantly associated with the development of GDM and shows potential for use as a predictive marker for GDM.
    Matched MeSH terms: Interleukin-10/genetics*
  4. Sam SS, Teoh BT, AbuBakar S
    Genet. Mol. Res., 2015;14(2):3257-63.
    PMID: 25966091 DOI: 10.4238/2015.April.13.4
    Inheritance of polymorphisms in the interleukin (IL)-10 promoter and IL-12B genes, which influence cytokine production and activities, may define the balance in T helper response in infection and autoimmune diseases. In the present study, we investigated the distribution of the IL-10 promoter and IL-12B gene polymorphisms in a multiethnic Malaysian population. Overall, our findings suggest that the IL-12B and IL-10 -592 genotypes were distributed homogenously across all major ethnic groups, including Malays, Chinese, and Indians, except for polymorphisms at IL-10 -1082. At this gene locus, the ethnic Chinese showed a significantly lower allele frequency of -1082G (2.1%) compared to the Malay (12.2%) and Indian (15.3%) populations. Results for the IL-12B and IL-10 gene polymorphisms were consistent with those reported for the Asian population, but markedly different from those of the African and Caucasian populations. Our findings suggest that there are specific genetic variations between different ethnic groups, which should be examined in all gene population-based association studies.
    Matched MeSH terms: Interleukin-10/genetics*
  5. Wong HC, Ooi Y, Pulikkotil SJ, Naing C
    BMC Oral Health, 2018 10 22;18(1):171.
    PMID: 30348144 DOI: 10.1186/s12903-018-0637-9
    BACKGROUND: Periodontitis is a major oral health problem and it is considered as one of the reasons for tooth loss in developing and developed nations. The objective of the current review was to investigate the association between IL10 polymorphisms - 1082 A > G (rs1800896), -819C > T (rs1800871), - 592 A > C (rs1800872) and the risk of either chronic periodontitis or aggressive periodontitis.

    METHODS: This is a meta- analysis study, following the preferred reporting items for systematic reviews and meta- analyses (PRISMA). Relevant studies were searched in the health related electronic databases. Methodological quality of the included studies were assessed using the Newcastle-Ottawa Scale. For individual studies, odds ratio (OR) and its 95%confidence interval (CI) were calculated to assess the strength of association between IL10 polymorphisms (- 1082 A > G, -819C > T, - 592 A > C) and the risk of periodontitis. For pooling of the estimates across studies included, the summary OR and its 95% CIs were calculated with random-effects model. The pooled estimates were done under four genetic models such as the allelic contrast model, the recessive model, the dominant model and the additive model. Trial sequential analysis (TSA) was done for estimation of the required information size for this meta-analysis study.

    RESULTS: Sixteen studies were identified for this review. The included studies were assessed to be of moderate to good methodological quality. A significant association between polymorphism of IL10-1082 A > G polymorphism and the risk of chronic periodontitis in the non-Asian populations was observed only in the recessive model (OR,1.42; 95% CI:1.11, 1.8,I2: 43%). The significant associations between - 592 A > C polymorphism and the risk of aggressive periodontitis in the non-Asian populations were observed in particular genetic models such as allele contrast (OR, 4.34; 95%CI:1.87,10.07,I2: 65%) and recessive models (OR, 2.1; 95% CI:1.16, 3.82,I2: 0%). The TSA plot revealed that the required information size for evidence of effect was sufficient to draw a conclusion.

    CONCLUSIONS: This meta-analysis suggested that the IL10-1082 A > G polymorphism was associated with chronic periodontitis CP risk in non-Asians. Thus, in order to further establish the associations between IL10 (- 819 C > T, - 592 A > C) in Asian populations, future studies should include larger sample sizes with multi-ethnic groups.

    Matched MeSH terms: Interleukin-10/genetics*
  6. Lee WS, Ng RT, Chan KW, Lau YL
    World J Gastroenterol, 2016 Dec 28;22(48):10653-10662.
    PMID: 28082818 DOI: 10.3748/wjg.v22.i48.10653
    AIM: Infantile-onset inflammatory bowel disease (IO-IBD) with the onset of disease before 12 mo of age, is a different disease entity from childhood IBD. We aimed to describe the clinical features, outcome and role of mutation in interleukin-10 (IL-10) and interleukin-10 receptors (IL-10R) in Asian children with IO-IBD.

    METHODS: All cases of IO-IBD, defined as onset of disease before 12 mo of age, seen at University Malaya Medical Center, Malaysia were reviewed. We performed mutational analysis for IL10 and IL10R genes in patients with presenting clinical features of Crohn's disease (CD).

    RESULTS: Six [13%; CD = 3, ulcerative colitis (UC) = 2, IBD-unclassified (IBD-U) = 1] of the 48 children (CD = 25; UC = 23) with IBD have IO-IBD. At final review [median (range) duration of follow-up: 6.5 (3.0-20) years], three patients were in remission without immunosuppression [one each for post-colostomy (IBD-U), after standard immunosuppression (CD), and after total colectomy (UC)]. Three patients were on immunosuppression: one (UC) was in remission while two (both CD) had persistent disease. As compared with later-onset disease, IO-IBD were more likely to present with bloody diarrhea (100% vs 55%, P = 0.039) but were similar in terms of an associated autoimmune liver disease (0% vs 19%, P = 0.31), requiring biologics therapy (50% vs 36%, P = 0.40), surgery (50% vs 29%, P = 0.27), or achieving remission (50% vs 64%, P = 0.40). No mutations in either IL10 or IL10R in the three patients with CD and the only patient with IBD-U were identified.

    CONCLUSION: The clinical features of IO-IBD in this Asian cohort of children who were negative for IL-10 or IL-10R mutations were variable. As compared to childhood IBD with onset of disease after 12 mo of age, IO-IBD achieved remission at a similar rate.

    Matched MeSH terms: Interleukin-10/genetics*; Receptors, Interleukin-10/genetics*
  7. Hee CS, Gun SC, Naidu R, Das Gupta E, Somnath SD, Radhakrishnan AK
    Mod Rheumatol, 2007;17(5):429-35.
    PMID: 17929139 DOI: 10.1007/s10165-007-0612-9
    In this study, three single nucleotide polymorphisms (SNPs) located within the promoter of the human interleukin (IL)-10 gene [rs1800896 (position: -1087G>A), rs1800871 (position: -824C>T) and rs1800872 (position: -597C>A)] were investigated in 84 rheumatoid arthritis (RA) patients and 95 age- and sex-matched healthy subjects using polymerase chain reaction-restriction fragment length polymorphism method. Production of IL-10 by peripheral blood lymphocytes from the RA patients and healthy subjects cultured in the presence of Concanavalin A (Con A) was determined by using enzyme-linked immunosorbent assay. The results show that the distribution of the IL-10 genotypes did not differ significantly between RA patients and healthy subjects (P>0.05). However, a significant difference was observed in allele frequencies of -824CT, -824TT, -597CA, and -597AA between the RA patients and healthy volunteers (P=0.04). The -1087A/-824T/-597A (ATA) haplotype, which comprises all mutant alleles, was associated with lower IL-10 production when compared with the other haplotypes. In contrast, the RA patients who did not display the ATA haplotype produced significantly higher levels of IL-10 when compared with those carrying either one (P=0.012) or two (P=0.005) ATA haplotypes. Our findings suggest that there is an association between SNPs in the promoter of the human IL-10 gene and susceptibility to RA.
    Study site: Hospital Tuanku Ja’afar, (Hospital Seremban), Seremban, Negeri Sembilan, Malaysia
    Matched MeSH terms: Interleukin-10/genetics*
  8. Sharif OM, Hassan R, Mohammed Basbaeen AA, Mohmed AH, Ibrahim IK
    Asian Pac J Cancer Prev, 2019 07 01;20(7):1939-1943.
    PMID: 31350948 DOI: 10.31557/APJCP.2019.20.7.1939
    Background: Interleukin-10 (IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenicfunctions
    and may have both tumor-promoting and -inhibiting properties. We examined the association
    between a single nucleotide polymorphism (SNP) in IL-10 -1082G/A (rs1800896) in Sudanese acute myeloid leukemia
    (AML) patients and to assess the association between polymorphisms in IL-10 -1082G/A (rs1800896) and the
    hematological profile in Sudanese patients with AML. Methods: A total of 30 patients with acute myeloid leukemia
    and 30 control subjects were enrolled in this study. Blood samples were collected from all patients in EDTA containing
    tubes. Genomic DNA was extracted from all blood samples using salting out method. The genotypic variants of
    IL-10 (-1082G/A) polymorphism were detected by allele specific-PCR. Results: We found that (36.7%) of patients have
    homogenous GG genotype, (43.3%) have heterogeneous GA genotype and (20.0%) have AA genotype. GA genotype
    was significantly associated with higher risk of AML compared with the homozygous Genotypes (GG and AA), there is
    no association between IL-10 (-1082G/A) polymorphism and AML sub-type, gender, age group, mean of hematological
    parameters. Conclusion: Our study concluded that GA genotype of IL-10 -1082G/A (rs1800896) polymorphism is a
    risk factor for AML and G allele is insignificantly higher than A allele in AML patient. No association between IL-10
    (-1082G/A) polymorphism and AML sub-type, gender, age group, mean of hematological parameters.
    Matched MeSH terms: Interleukin-10/genetics*
  9. Lim YY, Chin YM, Tai MC, Fani S, Chang KM, Ong TC, et al.
    Leuk Lymphoma, 2015 Jan;56(1):163-8.
    PMID: 24684230 DOI: 10.3109/10428194.2014.907895
    We evaluated the association of two IL10 single nucleotide polymorphisms (SNPs) (rs1800896 and rs1800871) with non-Hodgkin lymphoma (NHL) risk in the three major races of the Malaysian population (Malay, Chinese and Indian; 317 cases and 330 controls). Our initial screening demonstrated that rs1800871 but not rs1800896 was significantly associated with increased NHL risk in Malays (pMalay-Rec = 0.007) and Chinese only (pChinese-Rec = 0.039). Subsequent combined analysis of the Malay and Chinese revealed significant association of rs1800871 with all (ALL) NHL subtypes (pMeta-ALL-NHL-Rec = 0.001), ALL B-cell subtypes (pMeta-ALL-B-cell-Rec = 0.003), diffuse large B-cell lymphoma (DLBCL) subtype (pMeta-DLBCL-Rec = 0.002) and ALL T-cell subtypes (pMeta-ALL-T-cell-Rec = 0.031). SNP rs1800896 showed increased risk only in follicular lymphoma (FL) (pMeta-FL-Dom = 0.0004). We also detected a male-specific association of rs1800871 with increased NHL risk (pMeta-Male-ALL-NHL-Rec = 0.006) in the combined analysis. To our knowledge, this is the first report on the association of IL10 promoter SNPs with NHL susceptibility in the three major races of Malaysia.
    Matched MeSH terms: Interleukin-10/genetics*
  10. Sam SS, Teoh BT, Chinna K, AbuBakar S
    Int J Med Sci, 2015;12(2):177-86.
    PMID: 25589894 DOI: 10.7150/ijms.8988
    Dengue virus (DENV) infection usually presents with mild self-limiting dengue fever (DF). Few however, would present with the more severe form of the disease, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). In the present study, the association between IL-12B, IL-10 and TNF-α gene polymorphisms and dengue severity was investigated.
    METHODS: A case-control study was performed on a total of 120 unrelated controls, 86 DF patients and 196 DHF/DSS patients. The polymorphisms in IL-12B, IL-10 and TNF-α genes were genotyped using PCR-RFLP and PCR-sequencing methods.
    RESULTS: A protective association of TNF-α -308A allele and -308GA genotype against DHF/DSS was observed, while TNF-α -238A allele and -238GA genotype were associated with DHF/DSS. A combination of TNF-α -308GA+AA genotype and IL-10 non-GCC haplotypes, IL-12B pro homozygotes (pro1/pro1, pro2/pro2) and IL-12B 3'UTR AC were significantly correlated with protective effects against DHF/DSS. An association between the cytokine gene polymorphisms and protection against the clinical features of severe dengue including thrombocytopenia and increased liver enzymes was observed in this study.
    CONCLUSION: The overall findings of the study support the correlation of high-producer TNF-α genotypes combined with low-producer IL-10 haplotypes and IL-12B genotypes in reduced risk of DHF/DSS.
    KEYWORDS: Infectious disease; cytokine; dengue; genetics; polymorphism.; tropical
    Matched MeSH terms: Interleukin-10/genetics
  11. Goud EVSS, Malleedi S, Ramanathan A, Wong GR, Hwei Ern BT, Yean GY, et al.
    Asian Pac J Cancer Prev, 2019 Mar 26;20(3):935-941.
    PMID: 30912418
    Background: Interleukin-10 (IL10) genotypes have been closely correlated to the susceptibility for oral squamous cell
    carcinoma. More than half of oral cancers in the world occur in Asia with estimated 168,850 new cases were diagnosed
    in this geographical region alone. Considering the rising numbers of oral cancer cases in Malaysia, association of IL10
    A1082G gene polymorphism was correlated. Methodology: 41 oral squamous cell carcinoma (OSCC) cases and 48
    healthy controls of comparable age, gender, and with habits like smoking, alcohol consumption and betel quid chewing
    were selected. In this case-control study, samples were collected from the Oral Cancer Research and Coordinating
    Centre (OCRCC), Faculty of Dentistry, University of Malaya, Malaysia. Genotyping conditions were evaluated by
    polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). The PCR products were subjected
    to digestion by MnlI enzyme (NEB, UK) to screen for the IL10 A-1082G. Digested DNA products were analyzed by
    electrophoresis on 4% (w/v) agarose gel, stained with ethidium bromide and imaged under UV illumination. Chi-square
    test and Fisher’s Exact test were used in statistical analysis. Results: AG genotypes were present in 81.3% and 86.0% of
    healthy control and OSCC cases respectively (OR=0.468, 95% CI=0.133-1.653). No significant association was found
    between IL10 A1082G polymorphism with risk habits, clinico-pathological parameters and 5-years overall survival.
    The findings also show no significant correlation between the IL10 genotype and features of OSCC within the case
    group as measured by tumor size, lymph node involvement, stage, invasive front, grading, depth, pattern of invasion.
    Conclusion: This study suggests that functional polymorphism AG of IL10 A1082G may have no influence with OSCC
    susceptibility. However, further investigation with larger sample sizes can be conducted to provide additional evidence
    to support the lack of association of IL10 A1082G polymorphism in oral cancer.
    Matched MeSH terms: Interleukin-10/genetics*
  12. Mohamed SIA, Jantan I, Nafiah MA, Seyed MA, Chan KM
    BMC Complement Altern Med, 2018 Aug 06;18(1):232.
    PMID: 30081891 DOI: 10.1186/s12906-018-2296-4
    BACKGROUND: Dendritic cells (DCs) are unique antigen presenting cells (APC) which play a pivotal role in immunotherapy and induction of an effective immune response against tumors. In the present study, 80% ethanol extract of Phyllanthus amarus was used to generate tumor lysate (TLY) derived from HCT 116 and MCF-7 cancer cell lines via induction of apoptosis. Monocyte-derived DCs were generated ex vivo from the adherent population of peripheral blood mononuclear cells (PBMCs). The generated TLY were used to impulse DCs to investigate its effect on their cellular immune functions including antigen presentation capacity, phagocytic activity, chemotaxis capacity, T-cell proliferation and cytokines release.

    METHODS: The effect of P. amarus-generated TLY on DCs maturation was evaluated by determination of MHC class I, II and CD 11c expression as well as the co-stimulatory molecules CD 83 and 86 by using flow cytometry. The phagocytic capacity of TLY-pulsed DCs was investigated through FITC-dextran uptake by using flow cytometry. The effect on the cytokines release including IL-12, IL-6 and IL-10 was elucidated by using ELISA. The migration capacity and T cell proliferation activity of pulsed DCs were measured. The relative gene expression levels of cytokines were determined by using qRT-PCR. The major constituents of P. amarus extract were qualitatively and quantitatively analyzed by using validated reversed-phase high performance liquid chromatography (HPLC) methods.

    RESULTS: P. amarus-generated TLY significantly up-regulated the expression levels of MHC class I, CD 11 c, CD 83 and 86 in pulsed DCs. The release of interleukin IL-12 and IL-6 was enhanced by TLY-DCs at a ratio of 1 DC: 3 tumor apoptotic bodies (APO), however, the release of IL-10 was suppressed. The migration ability as well as allogeneic T-cell proliferation activities of loaded DCs were significantly enhanced, but their phagocytic capacity was highly attenuated. The gene expression profiles for IL-12 and IL-6 of DCs showed increase in their mRNA gene expression in TLY pulsed DCs versus unloaded and LPS-treated only DCs.

    CONCLUSION: The effect of P. amarus-generated TLY on the immune effector mechanisms of DCs verified its potential to induce an in vitro anti-tumor immune response against the recognized tumor antigen.

    Matched MeSH terms: Interleukin-10/genetics
  13. Ali AH, Sudi S, Basir R, Embi N, Sidek HM
    J Med Food, 2017 Feb;20(2):152-161.
    PMID: 28146408 DOI: 10.1089/jmf.2016.3813
    Curcumin, a bioactive compound in Curcuma longa, exhibits various pharmacological activities, including antimalarial effects. In silico docking simulation studies suggest that curcumin possesses glycogen synthase kinase-3β (GSK3β)-inhibitory properties. The involvement of GSK3 in the antimalarial effects in vivo is yet to be demonstrated. In this study, we aimed to evaluate whether the antimalarial effects of curcumin involve phosphorylation of host GSK3β. Intraperitoneal administration of curcumin into Plasmodium berghei NK65-infected mice resulted in dose-dependent chemosuppression of parasitemia development. At the highest dose tested (30 mg/kg body weight), both therapeutic and prophylactic administrations of curcumin resulted in suppression exceeding 50% and improved median survival time of infected mice compared to control. Western analysis revealed a 5.5-fold (therapeutic group) and 1.8-fold (prophylactic group) increase in phosphorylation of Ser 9 GSK3β and 1.6-fold (therapeutic group) and 1.7-fold (prophylactic group) increase in Ser 473 Akt in liver of curcumin-treated infected animals. Following P. berghei infection, levels of pro- and anti-inflammatory cytokines, tumor necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-10, and IL-4 were elevated by 7.5-, 35.0-, 33.0-, and 2.2-fold, respectively. Curcumin treatment (therapeutic) caused a significant decrease (by 6.0- and 2.0-fold, respectively) in serum TNF-α and IFN-γ level, while IL-10 and IL-4 were elevated (by 1.4- and 1.8-fold). Findings from the present study demonstrate for the first time that the antimalarial action of curcumin involved inhibition of GSK3β.
    Matched MeSH terms: Interleukin-10/genetics
  14. Islam MA, Kundu S, Hassan R
    Curr Gene Ther, 2020;19(6):376-385.
    PMID: 32141417 DOI: 10.2174/1566523220666200306092556
    Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.
    Matched MeSH terms: Interleukin-10/genetics
  15. Sarkar S, Leo BF, Carranza C, Chen S, Rivas-Santiago C, Porter AE, et al.
    PLoS One, 2015;10(11):e0143077.
    PMID: 26580078 DOI: 10.1371/journal.pone.0143077
    Exposure to silver nanoparticles (AgNP) used in consumer products carries potential health risks including increased susceptibility to infectious pathogens. Systematic assessments of antimicrobial macrophage immune responses in the context of AgNP exposure are important because uptake of AgNP by macrophages may lead to alterations of innate immune cell functions. In this study we examined the effects of exposure to AgNP with different particle sizes (20 and 110 nm diameters) and surface chemistry (citrate or polyvinlypyrrolidone capping) on cellular toxicity and innate immune responses against Mycobacterium tuberculosis (M.tb) by human monocyte-derived macrophages (MDM). Exposures of MDM to AgNP significantly reduced cellular viability, increased IL8 and decreased IL10 mRNA expression. Exposure of M.tb-infected MDM to AgNP suppressed M.tb-induced expression of IL1B, IL10, and TNFA mRNA. Furthermore, M.tb-induced IL-1β, a cytokine critical for host resistance to M.tb, was inhibited by AgNP but not by carbon black particles indicating that the observed immunosuppressive effects of AgNP are particle specific. Suppressive effects of AgNP on the M.tb-induced host immune responses were in part due to AgNP-mediated interferences with the TLR signaling pathways that culminate in the activation of the transcription factor NF-κB. AgNP exposure suppressed M.tb-induced expression of a subset of NF-κB mediated genes (CSF2, CSF3, IFNG, IL1A, IL1B, IL6, IL10, TNFA, NFKB1A). In addition, AgNP exposure increased the expression of HSPA1A mRNA and the corresponding stress-induced Hsp72 protein. Up-regulation of Hsp72 by AgNP can suppress M.tb-induced NF-κB activation and host immune responses. The observed ability of AgNP to modulate infectious pathogen-induced immune responses has important public health implications.
    Matched MeSH terms: Interleukin-10/genetics
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