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Thymoquinone inhibits TNF‐α‐induced pro‐inflammatory mediators in Rheumatoid arthritis synovial fibroblasts in vitro
Author(s) -
Umar Sadiq,
Hedaya Omar,
Agere Solomon,
Ahmed Salahuddin
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.393.8
Subject(s) - thymoquinone , p38 mitogen activated protein kinases , tumor necrosis factor alpha , protein kinase b , proinflammatory cytokine , pharmacology , mapk/erk pathway , cytokine , chemistry , signal transduction , inflammation , medicine , cancer research , immunology , biochemistry , antioxidant
Rheumatoid arthritis (RA) is an autoimmune disease in which cytokine such as tumor necrosis factor‐α (TNF‐α), activate synovial fibroblast (FLS) that results in inflammation and activate joint destruction. In this study using RA‐FLS, we investigate the efficacy of thymoquinone (TQ), a phytochemical found in Nigella sativa, in inhibiting TNF‐α induced proinflammatory mediators. RA‐FLS were pretreated with TQ (1–5 µM) for 2 hours followed by TNF‐α stimulation (30 mins or 24 hours). Conditioned medium was used for the quantification of IL‐6 and IL‐8 by ELISA and cell lysates were prepared for the analysis of adhesion molecule (ICAM‐1 and VCAM‐1) and mitogen‐activated protein kinases. Pretreatment of TQ inhibited the ability of TNF‐α to induce IL‐6 and IL‐8 production in RA synovial fibroblasts in a dose‐dependent manner (p<0.01). We also observed a marked inhibition in TNF‐α induced ICAM‐1 and VCAM‐1 expression by TQ (p<0.01). Evaluation of the signaling pathways using the inhibitors of p38(SB203580), JNK(SP600125),ERK(PD98059) and AKT (LY294001) showed that p38 and JNK played an important role in regulating TNF‐α induced IL‐6 and IL‐8 production, whereas p38 and AKT were involved in regulating ICAM‐1 and VCAM‐1 expression by TNF‐α stimulation in RA‐FLS (p<0.05). TQ was found to selectively inhibit TNF‐induced phosphorylation of p38 and JNK in a dose‐dependent manner. The results of the study show that TQ interferes with TNF‐α signaling pathways to regulate IL‐6 and IL8 production, and ICAM‐1/VCAM‐1 expression in RA‐FLS. Thus,TQ may be of potential therapeutic value in regulating inflammation and synovial invasion in RA.