Tangeretin inhibits IL-1β induced proliferation of rheumatoid synovial fibroblasts and the production of COX-2, PGE2 and MMPs via modulation of p38 MAPK/ERK/JNK pathways

Abstract

The study aimed to determine the effect of tangeretin in inhibiting the interleukin-1 (IL-1 )-induced proliferation of RASFs and suppression of the production of inflammatory mediators. RASFs were isolated from synovial tissue obtained from patients with RA during knee arthroscopy. The cells were exposed to IL-1 (1.0 ng/mL) and/ or tangeretin (50 or 100 µM). Cell viability was assessed following treatments. Expressions of MMPs and COX-2 were analysed by real-time PCR and western blotting. Production of prostaglandin E2 (PGE2) by RASFs were analysed by ELISA. Expressions of mitogen activated protein kinases (MAPKs) and nuclear factor-kB (NF-kB) were assessed by western blotting. Tangeretin significantly inhibited the proliferation of RASFs, as well as down-regulated the expression of MMP-1, MMP-3 and COX-2 mRNA and protein and also the phosphorylation of ERK, p38 and JNK. Raised level of expression of NF-κB and PGE2 induced by IL-1 was reduced by tangeretin. Results indicate that tangeretin was effective in inhibiting the synovial fibroblast proliferation, as well regulated MMPs, COX-2, PGE2 via modulation of p38 MAPK, ERK and JNK pathways. Article Info

Beneficial Effects of Citrus-Derived Polymethoxylated Flavones for Central Nervous System Disorders

“…Tangerine peel extract, which abundantly contains tangeretin, suppressed LPS-induced proinflammatory cytokine expression such as that of TNF-α, IL-1βand IL-6, and NO in the BV2 microglia culture system [ 143 ]. The anti-inflammatory effect of tangeretin was also investigated in rheumatoid synovial fibroblasts (RASFs) [ 144 ]. Tangeretin remarkably suppressed RASFs proliferation and downregulated the expression of MMP-1, MMP-3, and COX-2 levles and the phosphorylation of JNK, p38, and ERK.…”

“…Tangeretin remarkably suppressed RASFs proliferation and downregulated the expression of MMP-1, MMP-3, and COX-2 levles and the phosphorylation of JNK, p38, and ERK. Tangeretin also reduced the elevated expression levels of PGE 2 and NF-κB caused by IL-1 [ 144 ]. These results support further investigation of tangeretin’s therapeutic potential and molecular action mechanism regarding neuroinflammation and neurological diseases accompanying microglial activation.…”

Global trends in research of fibroblasts associated with rheumatoid diseases in the 21st century: A bibliometric analysis

“…A variety of cytokines may eventually increase the invasiveness and destructiveness of FLSs by activating transcription factors such as NF-kB (nuclear factor kappa B) and MAPK (mitogen-activated protein kinase), also representing two important intracellular signaling pathways. For example, IL-1 induces the gene expression of collagenase through the MAPK signaling pathway, and JNK is a key signal molecule in the MAPK signaling pathway (60). Therefore, therapy targeting JNK may have decent efficacy.…”