Arthritis & Rheumatism, Volume 62,
November 2010 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Atlanta, Georgia November 6-11, 2010.
Post-Transcriptional Regulation of IL-6 Production by Zc3h12a in Fibroblast-Like Synovial Cells.
Koga, Tomohiro, Yamasaki, Satoshi, Okada, Akitomo, Kawashiri, Shin-ya, Nakamura, Hideki, Kawakami, Atsushi, Eguchi, Katsumi
Zc3h12a is a RNA binding protein with a CCCH-type finger motif, known to regulate mRNA metabolism. Previous reports suggest that Zc3h12a acts as a negative regulator of inflammatory processes because it is engaged in the degradation of IL-6 We investigate the effect of Zc3h12a on IL-6 production in fibroblast-like synovial cells (FLS) from rheumatoid arthritis (RA) patients.
The expression of Zc3h12a in FLS was determined by western blot and polymerase chain reaction. To knock down the expression of Zc3h12a in FLS, siRNA for Zc3h12a was transfected by lipofection method. The supernatants were collected after the siRNA transfection for the quantification of IL-6 production. Cell proliferation was analyzed by the Cell Counting Kit-8 assay after Zc3h12a knock down.
Protein and mRNA for Zc3h12a were demonstrated in all the FLS from RA patients. Zc3h12a transcripts were induced by LPS and IL-1b in FLS. The production of IL-6 as well as its transcripts expression was significantly increased by knocking down of Zc3h12a. Proliferation of Zc3h12a knocked down FLS was significantly promoted in the presence of recombinant soluble IL-6 receptor (sIL-6R). Knocking down of Zc3h12a also induced the activation of signal tranducer and activator of transcription 3 (STAT3).
Our data suggests that Zc3h12a is a novel IL-6 regulator in FLS, which may be involved in the progression of RA.
To cite this abstract, please use the following information:
Koga, Tomohiro, Yamasaki, Satoshi, Okada, Akitomo, Kawashiri, Shin-ya, Nakamura, Hideki, Kawakami, Atsushi, et al; Post-Transcriptional Regulation of IL-6 Production by Zc3h12a in Fibroblast-Like Synovial Cells. [abstract]. Arthritis Rheum 2010;62 Suppl 10 :364