Sinomenine reduces invasion and migration ability in fibroblast-like synoviocytes cells co-cultured with activated human monocytic THP-1 cells by inhibiting the expression of MMP-2, MMP-9, CD147

Abstract

CD147 expressed by monocytes, macrophages, and synoviocytes cells can stimulate the production of matrix metalloproteinases (MMPs) associated with the development of rheumatoid arthritis (RA). We investigated the effects of Sinomenine (SIN) on invasion and migration ability and gene expression of CD147, MMP-2, MMP-9 of fibroblast-like synoviocytes cells (FLS) co-cultured with activated human monocytic THP-1 cells (A-THP-1) in vitro. SIN is a pure alkaloid extracted from the Chinese medical plant Sinomenium acutum. FLS cells were co-cultured with THP-1 cells which were induced to differentiate into macrophages with phorbol 12-myristate 13-acetate (PMA). Cells were treated with different concentrations of SIN. Invasion and migration ability of cells was tested by transwell assays. Western blot analysis and zymographic analysis were adopted to detect the expression of CD147 and MMPs, respectively. RT-PCR was used to determine the expression of mRNA of CD147, MMP-2, and MMP-9. The invasion and migration ability of the co-cultured cells was significantly inhibited by SIN in a concentration-dependent fashion, and at the same time, the levels of CD147, MMP-2, MMP-9 were markedly down-regulated. This inhibitory effect was most notable at concentrations of 0.25 and 1.00 mM (P < 0.01). Our results point to a possible mechanism of SIN on treatment of RA is the inhibitory effect of SIN on cell invasion and migration ability, which strongly correlates with repressing the expression of CD147, MMP-2, and MMP-9.

Urokinase plasminogen activator and receptor promote collagen-induced arthritis through expression in hematopoietic cells

“…Additionally macrophages produce a spectrum of proteases (in addition to uPA) such as matrix metalloproteinases that drive tissue destruction in RA. [30][31][32] In CIA, macrophages play a preeminent role in driving disease. Targeting molecules that promote macrophage proliferation, accumulation or activation (eg, CSF-1, granulocytemacrophage colony-stimulating factor, TNF-a, IL-1b, and IL-6) [33][34][35][36][37][38][39][40] suppresses CIA in mice.…”

Hyperoside exerts anti-inflammatory and anti-arthritic effects in LPS-stimulated human fibroblast-like synoviocytes in vitro and in mice with collagen-induced arthritis

“…In this study, we also confirmed that hyperoside reduced the LPS-induced increase in production of TNFα, IL-1β, and IL-6 Over 20 members of the MMP family have been identified in humans to date. Elevated gene expression of MMPs is critical for the progression of RA [47,48] . LPS can stimulate FLS to secrete MMPs, and this induction is regulated at the transcriptional and translational levels [49] .…”

Sinomenine suppresses collagen-induced arthritis by reciprocal modulation of regulatory T cells and Th17 cells in gut-associated lymphoid tissues

“…When orally administered at the doses of 100 and 300 mg/kg, SIN could attenuate adjuvantinduced arthritis (AIA) in rat and collagen-induced arthritis (CIA) in mouse through suppressing the production of autoantibody and modulating Th1/Th2 response (Feng et al, 2007;Mu et al, 2013). In vitro mechanistic studies showed that SIN could suppress the activation of T lymphocytes, induce the apoptosis of macrophage, reduce antigen-induced activation of basophils, and hinder migration of synoviocytes at concentrations over 0.5 mM (He et al, 2005;Huang et al, 2008;Liu et al, 1994;Ou et al, 2011). Overall, the minimal effective concentration of SIN against immunity or inflammation effector cells is quite high.…”