Carvacrol suppresses inflammatory responses in rheumatoid arthritis fibroblast‐like synoviocytes

• Published in: Journal of cellular biochemistry 2019-05, Vol.120 (5), p.8169-8176
• Main Authors: Li, Yu, Xu, Jian‐zhong, Gu, Chen‐xi, Liu, Guan‐lei, Tian, Ke
• Format: Article
• Language: English
• Subjects: Arthritis; Assaying; Carvacrol; Cell growth; Cell migration; Cell proliferation; Cell viability; Cytokines; Extracellular signal-regulated kinase; Fibroblasts; fibroblast‐like synoviocytes (FLSs); Human behavior; Inflammation; Inflammatory response; Interleukins; JNK protein; Kinases; Lipopolysaccharides; Matrix metalloproteinases; MyD88 protein; Phenols; Rheumatoid arthritis; rheumatoid arthritis (RA); Synoviocytes; TLR4 protein; Toll-like receptors; Tumor necrosis factor-α
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.28098

Background Fibroblast‐like synoviocytes (FLSs) play an essential role in the chronic inflammatory process of rheumatoid arthritis (RA). Carvacrol is a natural monoterpenic phenol that retains significant anti‐inflammatory activity. However, the effect of carvacrol on inflammatory response in RA‐FLSs has not yet been reported. The present study aimed to investigate the role of carvacrol in lipopolysaccharides (LPS)‐induced inflammatory response in human RA‐FLSs. Methods Cell viability and proliferation were measured by MTT and Cell Counting Kit‐8 assays, respectively. The migration was detected by transwell assay. The production of inflammatory cytokines and matrix metalloproteinases (MMPs) were analyzed by enzyme‐linked immunosorbent assay. The expressions of toll‐like receptor 4 (TLR4), myeloid differentiation primary response 88 (MyD88), NF‐κB, p38, p‐p38, ERK1/2, p‐ERK1/2, c‐Jun N‐terminal kinase (JNK), and p‐JNK were detected by Western blot analysis. Results Carvacrol‐inhibited LPS‐induced cell proliferation and migration of RA‐FLSs. The production of inflammatory cytokines, including tumor necrosis factor alpha, interleukin (IL)− 6, and IL‐8, was reduced by carvacrol in LPS‐induced RA‐FLSs. Meanwhile, the induction of MMPs, including MMP‐1, MMP‐3, and MMP‐13, caused by LPS stimulation was inhibited by carvacrol in RA‐FLSs. Furthermore, carvacrol prevented LPS‐induced activation of the TLR4/MyD88/NF‐κB, p38, and ERK1/2 pathways in RA‐FLSs. Conclusions Carvacrol‐mitigated LPS‐induced cell proliferation, migration, and inflammation in RA‐FLSs. The TLR4/MyD88/NF‐κB, p38 and ERK1/2 pathways might be involved in the protective effect of carvacrol. Carvacrol‐mitigated LPS‐induced cell proliferation, migration, and inflammation in RA‐FLSs. The TLR4/MyD88/NF‐κB, p38, and ERK1/2 pathways might be involved in the protective effect of carvacrol.