Rheumatoid arthritis synovial fibroblasts (RASFs) are known to produce matrix metalloproteinases (MMPs) and cause joint destruction. The purpose of this study is to develop a potential medicine for rheumatoid arthritis (RA).
To this end, first, the MMPs inhibition factor was purified from an alkali-solubilized fraction of RJ (Apis mellifera) by C18 reverse-phase column chromatography and identified as 10-hydroxy-2-decenoic acid (10H2DA) by LTQ XL analysis. Next, Experimental test 10H2DA how to inhibited the activities of MMPs: with RASFs isolated from rheumatoid tissues by enzymatic digestion, cultures in monolayers were treated with 10H2DA (0.5mM, 1mM, and 2mM) or PBS for 2h followed by stimulation with TNF-alpha (10 ng/ml) for 2h, mRNA. Protein levels of MMP-1 and MMP-3 were measured by real-time PCR and enzyme-linked immunosorbent assay (ELISA), the DNA-binding activity of activator protein-1 (AP-1) and nuclear factor kappaB (NF-kappaB) by electrophoretic mobility shift assay (EMSA), and the protein kinase activity of p38, ERK and JNK by kinase assay.
The molecular investigation revealed that the 10H2DA-mediated suppression was likely to occur through blocking p38 kinase and c-Jun N-terminal kinase-AP-1 signaling pathways. In contrast, 10H2DA had no effect on extracellular signal-regulated kinase activity, NF-kappaB DNA-binding activity and IkappaBalpha degradation.
These results suggest that 10H2DA may be of potential therapeutic value in inhibiting joint destruction in RA.