Displaying publications 1 - 20 of 45 in total

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  1. Abdullah D, Ford TR, Papaioannou S, Nicholson J, McDonald F
    Biomaterials, 2002 Oct;23(19):4001-10.
    PMID: 12162333
    Biocompatibility of two variants of accelerated Portland cement (APC) were investigated in vitro by observing the cytomorphology of SaOS-2 osteosarcoma cells in the presence of test materials and the effect of these materials on the expression of markers of bone remodelling. Glass ionomer cement (GIC), mineral trioxide aggregate (MTA) and unmodified Portland cement (RC) were used for comparison. A direct contact assay was undertaken in four samples of each test material, collected at 12, 24, 48 and 72 h. Cell morphology was observed using scanning electron microscopy (SEM) and scored. Culture media were collected for cytokine quantification using enzyme-linked immunosorbent assay (ELISA). On SEM evaluation, healthy SaOS-2 cells were found adhering onto the surfaces of APC variant, RC and MTA. In contrast, rounded and dying cells were observed on GIC. Using ELISA, levels of interleukin (IL)-1beta, IL-6, IL-18 and OC were significantly higher in APC variants compared with controls and GIC (p<0.01), but these levels of cytokines were not statistically significant compared with MTA. The results of this study provide evidence that both APC variants are non-toxic and may have potential to promote bone healing. Further development of APC is indicated to produce a viable dental restorative material and possibly a material for orthopaedic
    Matched MeSH terms: Interleukin-6/metabolism
  2. Selim K, Hüseyin C, Ibrahim KH, Hasan BU, Kazim U, Hüseyin K
    Med J Malaysia, 2004 Aug;59(3):391-4.
    PMID: 15727386
    Several pharmacological agents have been found to alter systemic concentrations and/or the activity of different cytokines via a variety of mechanisms, including changes in biosynthesis, secretion, and/or stability. Pentoxifylline (PTX), which is a methylxanthine derivative for example, has multiple effects on the immune system, but inhibition of pro-inflammatory cytokine release predominates. In this study we aimed to evaluate the influence of PTX on plasma levels of tumor necrosis factor (TNF) alpha and interleukin (IL)-6 in newborn infants with sepsis. The study included 20 infants with neonatal sepsis. In all subjects blood samples for serum C-reactive protein, TNF alpha and IL-6 determinations were received before giving PTX and at the 12th and 24th hours following PTX. In addition, white blood cell was counted before giving PTX and on the 3rd and 7th day following PTX. The infants were randomly divided into two groups. Firstly, PTX was used in infants who were successively admitted to the clinic and the subsequent infants were accepted as a control group. Of 20 infants, 13 infants received PTX and seven infants did not. We did not find any difference in the leukocyte count, serum C-reactive protein level, TNF alpha and IL-6 levels between the two groups of patients (P>0.05). While three infants died in the group of receiving PTX, death was not recorded in the group of non-receiving PTX (P>0.05). Our findings showed that PTX treatment did not affect leukocyte counts, serum CRP levels, TNF alpha and IL-6 levels and death ratio in newborn infants with sepsis. The last result may be due to the fact that the number of patients in the study was very small. We think that more extensive and controlled studies should be performed about this subject.
    Matched MeSH terms: Interleukin-6/metabolism*
  3. Ahmad NS, Khalid BA, Luke DA, Ima Nirwana S
    Clin Exp Pharmacol Physiol, 2005 Sep;32(9):761-70.
    PMID: 16173934
    1. Free radicals generated by ferric nitrilotriacetate (FeNTA) can activate osteoclastic activity and this is associated with elevation of the bone resorbing cytokines interleukin (IL)-1 and IL-6. In the present study, we investigated the effects of 2 mg/kg FeNTA (2 mg iron/kg) on the levels of serum IL-1 and IL-6 with or without supplementation with a palm oil tocotrienol mixture or alpha-tocopherol acetate in Wistar rats. 2. The FeNTA was found to elevate levels of IL-1 and IL-6. Only the palm oil tocotrienol mixture at doses of 60 and 100 mg/kg was able to prevent FeNTA-induced increases in IL-1 (P < 0.01). Both the palm oil tocotrienol mixture and alpha-tocopherol acetate, at doses of 30, 60 and 100 mg/kg, were able to reduce FeNTA-induced increases in IL-6 (P < 0.05). Therefore, the palm oil tocotrienol mixture was better than pure alpha-tocopherol acetate in protecting bone against FeNTA (free radical)-induced elevation of bone-resorbing cytokines. 3. Supplementation with the palm oil tocotrienol mixture or alpha-tocopherol acetate at 100 mg/kg restored the reduction in serum osteocalcin levels due to ageing, as seen in the saline (control) group (P < 0.05). All doses of the palm oil tocotrienol mixture decreased urine deoxypyridinoline cross-link (DPD) significantly compared with the control group, whereas a trend for decreased urine DPD was only seen for doses of 60 mg/kg onwards of alpha-tocopherol acetate (P < 0.05). 4. Bone histomorphometric analyses have shown that FeNTA injections significantly lowered mean osteoblast number (P < 0.001) and the bone formation rate (P < 0.001), but raised osteoclast number (P < 0.05) and the ratio of eroded surface/bone surface (P < 0.001) compared with the saline (control) group. Supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent all these FeNTA-induced changes, but a similar dose of alpha-tocopherol acetate was found to be effective only for mean osteoclast number. Injections of FeNTA were also shown to reduce trabecular bone volume (P < 0.001) and trabecular thickness (P < 0.05), whereas only supplementation with 100 mg/kg palm oil tocotrienol mixture was able to prevent these FeNTA-induced changes.
    Matched MeSH terms: Interleukin-6/metabolism
  4. Chew MM, Gan SY, Khoo AS, Tan EL
    BMC Cancer, 2010;10:574.
    PMID: 20964870 DOI: 10.1186/1471-2407-10-574
    Nasopharyngeal carcinoma (NPC) is a type of neoplasm that is highly prevalent in East Asia and Africa with Epstein-Barr virus (EBV), genetic, and dietary factors implicated as possible aetiologic factors. Previous studies suggested the association of certain cytokines with the invasion and metastatic properties of NPC. The present study examined the roles of EBV latent membrane protein-1 (LMP1), interleukin-6 (IL-6), interleukin-10 (IL-10), transforming growth factor-beta 1 (TGF-β1) and laminin in the regulation of matrix-metalloproteinases (MMPs) and vascular endothelial growth factor (VEGF) in NPC. The effects of these factors on bmi-1, an oncogene, and ngx6, a tumour suppressor gene, were also investigated.
    Matched MeSH terms: Interleukin-6/metabolism
  5. Moktar NM, Yusof HM, Yahaya NH, Muhamad R, Das S
    Clin Ter, 2010;161(1):25-8.
    PMID: 20393674
    AIMS: The mRNA level for interleukin-6 (IL-6) is an important marker of osteoarthritis (OA). The present study aimed to investigate the level of IL-6 mRNA in the cartilage of OA knee while comparing it to the normal cartilage obtained from the same patient.
    MATERIALS AND METHODS: A total of 21 patients who underwent total knee replacement were recruited for this study. Sectioning of the destructive cartilage was performed in the medial part of the proximal tibiofemoral cartilage. The unaffected lateral part of the knee in the same patient, served as a control. The mRNA level for IL-6 was assessed using LightCycler 2.0 quantitative real-time polymerase chain reaction (qRT-PCR). actin mRNA was used as an endogenous control.
    RESULTS: Twelve out of 21 patients (57.1%) exhibited up regulation of IL-6 mRNA in the OA cartilage as compared to the normal cartilage. The rest of the patients (42.9%) showed down regulation of IL-6 mRNA. The statistical analysis showed there was insignificant level of IL-6 mRNA in the OA (1.91 +/- 0.45) as compared to the normal cartilage (1.13 +/- 0.44) (p > 0.05). The inter-individual variation in the level of IL-6 mRNA in the cartilage of idiopathic knee was in accordance with previous findings.
    CONCLUSIONS: These observations suggest IL-6 could also act as a catabolic agent in some patients or its expression might be influenced by other cytokines.
    Study site: Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), Kuala Lumpur, Malaysia
    Matched MeSH terms: Interleukin-6/metabolism*
  6. Abdelwahab SI, Abdul AB, Zain ZN, Hadi AH
    Int Immunopharmacol, 2012 Apr;12(4):594-602.
    PMID: 22330084 DOI: 10.1016/j.intimp.2012.01.014
    Interleukin-6 is one of the factors affecting sensitivity to cytotoxic agents. Therefore, the current study was designed to investigate the role of IL-6 and IL6 receptors in the cytotoxic effects of zerumbone in ovarian and cervical cancer cell lines (Caov-3 and HeLa, respectively). Exposure of both cancer cells to zerumbone or cisplatin demonstrated growth inhibition at a dose-dependent manner as determined by the MTT (3-[4,5-dimethylthiazol-2-yl]-2,Sdiphenyltetrazolium bromide) reduction assay. Both laser scanning confocal microscopy and TUNEL assay showed typical apoptotic features in treated cells. The studies conducted seems to suggest that zerumbone induces cell death by stimulating apoptosis better than cisplatin, based on the significantly higher percentage of apoptotic cells in zerumbone's treated cancer cells as compared to cisplatin. In addition, zerumbone and cisplatin arrest cancer cells at G2/M phase as analyzed by flow cytometry. Our results indicated that zerumbone significantly decreased the levels of IL-6 secreted by both cancer cells. In contrast, HeLa and Caov-3 cells were still sensitive to cisplatin and zerumbone, even in the presence of exogenous IL-6. However, membrane-bound IL-6 receptor is still intact after zerumbone treatment as demonstrated using an immune-fluorescence technique. This study concludes that the compound, zerumbone inhibits both cancer cell growth through the induction of apoptosis, arrests cell cycle at G2/M phase and inhibits the secretion levels of IL-6 in both cancer cells. Therefore, zerumbone is a potential candidate as a useful chemotherapeutic agent in treating both cervical and ovarian cancers in future.
    Matched MeSH terms: Interleukin-6/metabolism*
  7. Taha MM, Salga MS, Ali HM, Abdulla MA, Abdelwahab SI, Hadi AH
    J Ethnopharmacol, 2012 May 7;141(1):273-81.
    PMID: 22374081 DOI: 10.1016/j.jep.2012.02.030
    Turnera diffusa Willd. ex Schult. has been used for the treatment of several human disorders including peptic ulcer.
    Matched MeSH terms: Interleukin-6/metabolism
  8. Fonseka M, Ramasamy R, Tan BC, Seow HF
    Cell Biol Int, 2012 Sep;36(9):793-801.
    PMID: 22335239 DOI: 10.1042/CBI20110595
    hUCB-MSC (human umbilical cord blood-derived mesenchymal stem cells) offer an attractive alternative to bone marrow-derived MSC for cell-based therapy by being less invasive a source of biological material. We have evaluated the effect of hUCB-MSC on the proliferation of K562 (an erythromyeloblastoid cell line) and the cytokine secretion pattern of hUCB-MSC. Co-culturing of hUCB-MSC and K562 resulted in inhibition of proliferation of K562 in a dose-dependent manner. However, the anti-proliferative effect was reduced in transwells, suggesting the importance of direct cell-to-cell contact. hUCB-MSC inhibited proliferation of K562, arresting them in the G0 /G1 phase. NO (nitric oxide) was not involved in the hUCB-MSC-mediated tumour suppression. The presence of IL-6 (interleukin 6) and IL-8 were obvious in the hUCB-MSC conditioned media, but no significant increase was found in 29 other cytokines. Th1 cytokines, IFNα (interferon α), Th2 cytokine IL-4 and Th17 cytokine, IL-17 were not secreted by hUCB-MSC. There was an increase in the number of hUCB-MSC expressing the latent membrane-bound form of TGFβ1 co-cultured with K562. The anti-proliferative effect of hUCB-MSC was due to arrest of the growth of K562 in the G0 /G1 phase. The mechanisms underlying increased IL-6 and IL-8 secretion and LAP (latency-associated peptide; TGFβ1) by hUCB-MSC remains unknown.
    Matched MeSH terms: Interleukin-6/metabolism*
  9. Makpol S, Zainuddin A, Chua KH, Yusof YA, Ngah WZ
    Clinics (Sao Paulo), 2012;67(2):135-43.
    PMID: 22358238
    OBJECTIVE: Human diploid fibroblasts undergo a limited number of cellular divisions in culture and progressively reach a state of irreversible growth arrest, a process termed cellular aging. The beneficial effects of vitamin E in aging have been established, but studies to determine the mechanisms of these effects are ongoing. This study determined the molecular mechanism of γ-tocotrienol, a vitamin E homolog, in the prevention of cellular aging in human diploid fibroblasts using the expression of senescence-associated genes.

    METHODS: Primary cultures of young, pre-senescent, and senescent fibroblast cells were incubated with γ-tocotrienol for 24 h. The expression levels of ELN, COL1A1, MMP1, CCND1, RB1, and IL6 genes were determined using the quantitative real-time polymerase chain reaction. Cell cycle profiles were determined using a FACSCalibur Flow Cytometer.

    RESULTS: The cell cycle was arrested in the G(0)/G(1) phase, and the percentage of cells in S phase decreased with senescence. CCND1, RB1, MMP1, and IL6 were upregulated in senescent fibroblasts. A similar upregulation was not observed in young cells. Incubation with γ-tocotrienol decreased CCND1 and RB1 expression in senescent fibroblasts, decreased cell populations in the G(0)/G(1) phase and increased cell populations in the G(2)/M phase. γ-Tocotrienol treatment also upregulated ELN and COL1A1 and downregulated MMP1 and IL6 expression in young and senescent fibroblasts.

    CONCLUSION: γ-Tocotrienol prevented cellular aging in human diploid fibroblasts, which was indicated by the modulation of the cell cycle profile and senescence-associated gene expression.

    Matched MeSH terms: Interleukin-6/metabolism
  10. Zhang Y, Yan W, Collins MA, Bednar F, Rakshit S, Zetter BR, et al.
    Cancer Res, 2013 Oct 15;73(20):6359-74.
    PMID: 24097820 DOI: 10.1158/0008-5472.CAN-13-1558-T
    Pancreatic cancer, one of the deadliest human malignancies, is almost invariably associated with the presence of an oncogenic form of Kras. Mice expressing oncogenic Kras in the pancreas recapitulate the stepwise progression of the human disease. The inflammatory cytokine interleukin (IL)-6 is often expressed by multiple cell types within the tumor microenvironment. Here, we show that IL-6 is required for the maintenance and progression of pancreatic cancer precursor lesions. In fact, the lack of IL-6 completely ablates cancer progression even in presence of oncogenic Kras. Mechanistically, we show that IL-6 synergizes with oncogenic Kras to activate the reactive oxygen species detoxification program downstream of the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling cascade. In addition, IL-6 regulates the inflammatory microenvironment of pancreatic cancer throughout its progression, providing several signals that are essential for carcinogenesis. Thus, IL-6 emerges as a key player at all stages of pancreatic carcinogenesis and a potential therapeutic target.
    Matched MeSH terms: Interleukin-6/metabolism*
  11. Barathan M, Mariappan V, Shankar EM, Abdullah BJ, Goh KL, Vadivelu J
    Cell Death Dis, 2013;4:e697.
    PMID: 23807226 DOI: 10.1038/cddis.2013.219
    Photodynamic therapy (PDT) has emerged as a capable therapeutic modality for the treatment of cancer. PDT is a targeted cancer therapy that reportedly leads to tumor cell apoptosis and/or necrosis by facilitating the secretion of certain pro-inflammatory cytokines and expression of multiple apoptotic mediators in the tumor microenvironment. In addition, PDT also triggers oxidative stress that directs tumor cell killing and activation of inflammatory responses. However, the cellular and molecular mechanisms underlying the role of PDT in facilitating tumor cell apoptosis remain ambiguous. Here, we investigated the ability of PDT in association with hypericin (HY) to induce tumor cell apoptosis by facilitating the induction of reactive oxygen species (ROS) and secretion of Th1/Th2/Th17 cytokines in human hepatocellular liver carcinoma cell line (HepG2) cells. To discover if any apoptotic mediators were implicated in the enhancement of cell death of HY-PDT-treated tumor cells, selected gene profiling in response to HY-PDT treatment was implemented. Experimental results showed that interleukin (IL)-6 was significantly increased in all HY-PDT-treated cells, especially in 1 μg/ml HY-PDT, resulting in cell death. In addition, quantitative real-time PCR analysis revealed that the expression of apoptotic genes, such as BH3-interacting-domain death agonist (BID), cytochrome complex (CYT-C) and caspases (CASP3, 6, 7, 8 and 9) was remarkably higher in HY-PDT-treated HepG2 cells than the untreated HepG2 cells, entailing that tumor destruction of immune-mediated cell death occurs only in PDT-treated tumor cells. Hence, we showed that HY-PDT treatment induces apoptosis in HepG2 cells by facilitating cytotoxic ROS, and potentially recruits IL-6 and apoptosis mediators, providing additional hints for the existence of alternative mechanisms of anti-tumor immunity in hepatocellular carcinoma, which contribute to long-term suppression of tumor growth following PDT.
    Matched MeSH terms: Interleukin-6/metabolism
  12. Shu MH, Appleton D, Zandi K, AbuBakar S
    PMID: 23497105 DOI: 10.1186/1472-6882-13-61
    Gracilaria changii (Xia et Abbott) Abbott, Zhang et Xia, a red algae commonly found in the coastal areas of Malaysia is traditionally used for foods and for the treatment of various ailments including inflammation and gastric ailments. The aim of the study was to investigate anti-inflammatory, gastroprotective and anti-ulcerogenic activities of a mass spectrometry standardized methanolic extract of Gracilaria changii.
    Matched MeSH terms: Interleukin-6/metabolism
  13. Mehrbod P, Hair-Bejo M, Tengku Ibrahim TA, Omar AR, El Zowalaty M, Ajdari Z, et al.
    Int J Mol Med, 2014 Jul;34(1):61-73.
    PMID: 24788303 DOI: 10.3892/ijmm.2014.1761
    Influenza A virus is one of the most important health risks that lead to significant respiratory infections. Continuous antigenic changes and lack of promising vaccines are the reasons for the unsuccessful treatment of influenza. Statins are pleiotropic drugs that have recently served as anti-influenza agents due to their anti-inflammatory activity. In this study, the effect of simvastatin on influenza A-infected cells was investigated. Based on the MTT cytotoxicity test, hemagglutination (HA) assay and qPCR it was found that simvastatin maintained cell viability and decreased the viral load significantly as compared to virus-inoculated cells. The expression of important pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6 and interferon-γ), which was quantified using ELISA showed that simvastatin decreased the expression of pro-inflammatory cytokines to an average of 2-fold. Furthermore, the modulation of actin filament polymerization was determined using rhodamine staining. Endocytosis and autophagy processes were examined by detecting Rab and RhoA GTPase protein prenylation and LC3 lipidation using western blotting. The results showed that inhibiting GTPase and LC3 membrane localization using simvastatin inhibits influenza replication. Findings of this study provide evidence that modulation of RhoA, Rabs and LC3 may be the underlying mechanisms for the inhibitory effects of simvastatin as an anti-influenza compound.
    Matched MeSH terms: Interleukin-6/metabolism
  14. Bukhari SN, Lauro G, Jantan I, Bifulco G, Amjad MW
    Bioorg Med Chem, 2014 Aug 1;22(15):4151-61.
    PMID: 24938495 DOI: 10.1016/j.bmc.2014.05.052
    Arachidonic acid and its metabolites have generated high level of interest among researchers due to their vital role in inflammation. The inhibition of enzymes involved in arachidonic acid metabolism has been considered as synergistic anti-inflammatory effect. A series of novel α,β-unsaturated carbonyl based compounds were synthesized and evaluated for their inhibitory activity on secretory phospholipase A₂ (sPLA₂), cyclooxygenases (COX), soybean lipoxygenase (LOX) in addition to proinflammatory cytokines comprising IL-6 and TNF-α. Six α,β-unsaturated carbonyl based compounds (2, 3, 4, 12, 13 and 14) exhibited strong inhibition of sPLA₂ activity, with IC₅₀ values in the range of 2.19-8.76 μM. Nine compounds 1-4 and 10-14 displayed inhibition of COX-1 with IC₅₀ values ranging from 0.37 to 1.77 μM (lower than that of reference compound), whereas compounds 2, 10, 13 and 14 strongly inhibited the COX-2. The compounds 10-14 exhibited strong inhibitory activity against LOX enzyme. All compounds were evaluated for the inhibitory activities against LPS-induced TNF-α and IL-6 release in the macrophages. On the basis of screening results, five active compounds 3, 4, 12, 13 and 14 were found strong inhibitors of TNF-α and IL-6 release in a dose-dependent manner. Molecular docking experiments were performed to clarify the molecular aspects of the observed COX and LOX inhibitory activities of the investigated compounds. Present findings increases the possibility that these α,β-unsaturated carbonyl based compounds might serve as beneficial starting point for the design and development of improved anti-inflammatory agents.
    Matched MeSH terms: Interleukin-6/metabolism
  15. Zulkifli I, Najafi P, Nurfarahin AJ, Soleimani AF, Kumari S, Aryani AA, et al.
    Poult Sci, 2014 Dec;93(12):3112-8.
    PMID: 25306460 DOI: 10.3382/ps.2014-04099
    An experiment was conducted to determine the effect of corticosterone (CORT) administration on serum ovotransferrin (OVT), α1-acid glycoprotein (AGP), ceruloplasmin (CPN), and IL-6 concentrations, and brain heat shock protein (HSP) 70 expression in broiler chickens. From 14 to 20 d of age, equal numbers of birds were subjected to either (i) daily intramuscular injection with CORT in ethanol:saline (1:1, vol/vol) at 6 mg/kg of BW, or (ii) daily intramuscular injection with 0.5 mL ethanol:saline (1:1, vol/vol; control). Blood samples were collected before CORT treatment (14 d old), 3 and 7 d after CORT injections, and 4 d after cessation of CORT administration for determination of serum levels of CORT, OVT, AGP, CPN, and IL-6. Brain samples (whole cerebrum) were collected to measure HSP 70 density. Although CORT administration significantly increased feed intake, weight gain was significantly depressed. Administration of CORT also increased CORT, OVT, CPN, AGP, IL-6, and HSP 70 expression. Four days following cessation of CORT administration, OVT declined to the basal level but not CPN and AGP. In conclusion, an elevation in CORT can induce an acute-phase response and HSP 70 expression. Thus, APP and HSP 70 may be of value as indicators of stress in poultry.
    Matched MeSH terms: Interleukin-6/metabolism*
  16. Mahmood ND, Mamat SS, Kamisan FH, Yahya F, Kamarolzaman MF, Nasir N, et al.
    Biomed Res Int, 2014;2014:695678.
    PMID: 24868543 DOI: 10.1155/2014/695678
    Muntingia calabura L. is a tropical plant species that belongs to the Elaeocarpaceae family. The present study is aimed at determining the hepatoprotective activity of methanol extract of M. calabura leaves (MEMC) using two models of liver injury in rats. Rats were divided into five groups (n=6) and received 10% DMSO (negative control), 50 mg/kg N-acetylcysteine (NAC; positive control), or MEMC (50, 250, and 500 mg/kg) orally once daily for 7 days and on the 8th day were subjected to the hepatotoxic induction using paracetamol (PCM). The blood and liver tissues were collected and subjected to biochemical and microscopical analysis. The extract was also subjected to antioxidant study using the 2,2-diphenyl-1-picrylhydrazyl-(DPPH) and superoxide anion-radical scavenging assays. At the same time, oxygen radical antioxidant capacity (ORAC) and total phenolic content were also determined. From the histological observation, lymphocyte infiltration and marked necrosis were observed in PCM-treated groups (negative control), whereas maintenance of hepatic structure was observed in group pretreated with N-acetylcysteine and MEMC. Hepatotoxic rats pretreated with NAC or MEMC exhibited significant decrease (P<0.05) in ALT and AST enzymes level. Moreover, the extract also exhibited good antioxidant activity. In conclusion, MEMC exerts potential hepatoprotective activity that could be partly attributed to its antioxidant activity and, thus warrants further investigations.
    Matched MeSH terms: Interleukin-6/metabolism
  17. Razali FN, Ismail A, Abidin NZ, Shuib AS
    PLoS One, 2014;9(10):e108988.
    PMID: 25299340 DOI: 10.1371/journal.pone.0108988
    The polysaccharide fraction from Solanum nigrum Linne has been shown to have antitumor activity by enhancing the CD4+/CD8+ ratio of the T-lymphocyte subpopulation. In this study, we analyzed a polysaccharide extract of S. nigrum to determine its modulating effects on RAW 264.7 murine macrophage cells since macrophages play a key role in inducing both innate and adaptive immune responses. Crude polysaccharide was extracted from the stem of S. nigrum and subjected to ion-exchange chromatography to partially purify the extract. Five polysaccharide fractions were then subjected to a cytotoxicity assay and a nitric oxide production assay. To further analyze the ability of the fractionated polysaccharide extract to activate macrophages, the phagocytosis activity and cytokine production were also measured. The polysaccharide fractions were not cytotoxic, but all of the fractions induced nitric oxide in RAW 264.7 cells. Of the five fractions tested, SN-ppF3 was the least toxic and also induced the greatest amount of nitric oxide, which was comparable to the inducible nitric oxide synthase expression detected in the cell lysate. This fraction also significantly induced phagocytosis activity and stimulated the production of tumor necrosis factor-α and interleukin-6. Our study showed that fraction SN-ppF3 could classically activate macrophages. Macrophage induction may be the manner in which polysaccharides from S. nigrum are able to prevent tumor growth.
    Matched MeSH terms: Interleukin-6/metabolism
  18. Shawish HB, Wong WY, Wong YL, Loh SW, Looi CY, Hassandarvish P, et al.
    PLoS One, 2014;9(6):e100933.
    PMID: 24977407 DOI: 10.1371/journal.pone.0100933
    BACKGROUND: The biological properties of thiosemicarbazone have been widely reported. The incorporation of some transition metals such as Fe, Ni and Cu to thiosemicarbazone complexes is known to enhance its biological effects. In this study, we incorporated nickel(II) ions into thiosemicarbazone with N4-substitution groups H3L (H; H3L1, CH3; H3L2, C6H5; H3L3 and C2H5; H3L4) and examined its potential anti-inflammatory activity.

    METHODOLOGY/PRINCIPAL FINDINGS: Four ligands (1-4) and their respective nickel-containing complexes (5-8) were synthesized and characterized. The compounds synthesized were tested for their effects on NF-κB nuclear translocation, pro-inflammatory cytokines secretion and NF-κB transactivation activity. The active compound was further evaluated on its ability to suppress carrageenan-induced acute inflammation in vivo. A potential binding target of the active compound was also predicted by molecular docking analysis.

    CONCLUSIONS/SIGNIFICANCE: Among all synthesized compounds tested, we found that complex [Ni(H2L1)(PPh3)]Cl (5) (complex 5), potently inhibited IκBα degradation and NF-κB p65 nuclear translocation in LPS-stimulated RAW264.7 cells as well as TNFα-stimulated HeLa S3 cells. In addition, complex 5 significantly down-regulated LPS- or TNFα-induced transcription of NF-κB target genes, including genes that encode the pro-inflammatory cytokines TNFα, IFNβ and IL6. Luciferase reporter assays confirmed that complex 5 inhibited the transactivation activity of NF-κB. Furthermore, the anti-inflammatory effect of complex 5 was also supported by its suppressive effect on carrageenan-induced paw edema formation in wild type C57BL/6 mice. Interestingly, molecular docking study showed that complex 5 potentially interact with the active site of IKKβ. Taken together, we suggest complex 5 as a novel NF-κB inhibitor with potent anti-inflammatory effects.

    Matched MeSH terms: Interleukin-6/metabolism
  19. Prakash A, Kumar A, Ming LC, Mani V, Majeed AB
    J Mol Neurosci, 2015 Jul;56(3):739-50.
    PMID: 25854775 DOI: 10.1007/s12031-015-0508-7
    Alzheimer's disease (AD) is a neurodegenerative disease characterized by impaired memory function and oxidative damage. NO is a major signaling molecule produced in the central nervous system to modulate neurological activity through modulating nitric oxide synthase. Recently, PPAR-γ agonists have shown neuroprotective effects in neurodegenerative disorders. However, there have been only a few studies identifying mechanisms through which cognitive benefits may be exerted. The present study was designed to investigate the possible nitric oxide mechanism in the protective effect of pioglitazone against streptozotocin (STZ)-induced memory dysfunction. Wistar rats were intracerebroventricularly (ICV) injected with STZ. Then rats were treated with pioglitazone, NO modulators [L-arginine and nitro-L-arginine methyl ester (L-NAME)] for 21 days. Behavioral alterations were assessed in between the study period. Animals were sacrificed immediately after behavioral session, and mito-oxidative parameters, TNF-α, IL-6, and caspase-3 activity were measured. STZ-treated rats showed a memory deficit and significantly increased in mito-oxidative damage and inflammatory mediators and apoptosis in the hippocampus. Chronic treatment of pioglitazone significantly improved memory retention and attenuated mito-oxidative damage parameters, inflammatory markers, and apoptosis in STZ-treated rats. However, L-arginine pretreatment with lower dose of pioglitazone has not produced any protective effect as compared to per se. Furthermore, pretreatment of L-NAME significantly potentiated its protective effect, which indicates the involvement of nitric oxide for activation of PPAR-γ action. These results demonstrate that pioglitazone offers protection against STZ-induced memory dysfunction possibly due to its antioxidant, anti-inflammatory, and anti-apoptotic action mediating nitric oxide pathways and, therefore, could have a therapeutic potential in AD.
    Matched MeSH terms: Interleukin-6/metabolism
  20. Zulaziz N, Azhim A, Himeno N, Tanaka M, Satoh Y, Kinoshita M, et al.
    Hum. Cell, 2015 Oct;28(4):159-66.
    PMID: 25997703 DOI: 10.1007/s13577-015-0118-2
    Antibacterial photodynamic therapy (PDT) has come to attract attention as an alternative therapy for drug-resistant bacteria. Recent reports revealed that antibacterial PDT induces innate immune response and stimulates abundant cytokine secretion as a part of inflammatory responses. However, the underlying mechanism how antibacterial PDT interacts with immune cells responsible for cytokine secretion has not been well outlined. In this study, we aimed to clarify the difference in gene expression and cytokine secretion between combined culture of fibroblasts and macrophages and their independent cultures. SCRC-1008, mouse fibroblast cell line and J774, mouse macrophage-like cell line were co-cultured and PDT treatments with different parameters were carried out. After various incubation periods (1-24 h), cells and culture medium were collected, and mRNA and protein levels for cytokines were measured using real-time PCR and ELISA, respectively. Our results showed that fibroblasts and macrophages interact with each other to mediate the immune response. We propose that fibroblasts initially respond to PDT by expressing Hspa1b, which regulates the NF-κB pathway via Tlr2 and Tlr4. Activation of the NF-κB pathway then results in an enhanced secretion of pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β) and neutrophil chemoattractant MIP-2 and KC from macrophages.
    Matched MeSH terms: Interleukin-6/metabolism
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