title: Post-transcriptional regulation of IL-6 production by Zc3h12a in fibroblast-like synovial cells.
abstract: OBJECTIVE
  Zc3h12a is an RNA binding protein with a CCCH-type finger motif and is known to regulate mRNA metabolism. Previous reports suggest that Zc3h12a acts as a negative regulator of inflammatory processes because it is involved in the degradation of IL-6 mRNA. We investigate the effect of Zc3h12a on IL-6 production in fibroblast-like synovial cells (FLS) from rheumatoid arthritis (RA) patients.
  
  
  METHODS
  The expression of Zc3h12a in FLS was determined by polymerase chain reaction. To knock down Zc3h12a expression in FLS, siRNA for Zc3h12a was transfected by the lipofection method. The supernatants were collected after siRNA transfection for the quantification of IL-6 production. The phosphorylation of the signal transducer and activator of transcription 3 (STAT3) was examined by Western blotting. Cell proliferation was analysed by the Cell Counting Kit-8 assay after Zc3h12a knockdown.
  
  
  RESULTS
  mRNA for Zc3h12a were demonstrated in FLS from RA patients. Zc3h12a transcripts were induced by LPS or IL-1β in FLS. The production of IL-6 as well as its mRNA expression was significantly increased by the Zc3h12a knockdown. The Zc3h12a knockdown also induced the activation of STAT3, which the anti IL-6 receptor antibody inhibited. Proliferation of Zc3h12a-knockdown FLS increased significantly in the presence of recombinant soluble IL-6 receptor (sIL-6R).
  
  
  CONCLUSIONS
  Our data suggest that Zc3h12a is a novel IL-6 regulator in FLS, which may be involved in the progression of RA.
authors: Department of Immunology and Rheumatology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. tkoga@nagasaki-u.ac.jp
authors: Tomohiro
authors: T
authors: Koga
authors: Satoshi
authors: S
authors: Yamasaki
authors: Kiyoshi
authors: K
authors: Migita
authors: Junko
authors: J
authors: Kita
authors: Akitomo
authors: A
authors: Okada
authors: Shinya
authors: S
authors: Kawashiri
authors: Naoki
authors: N
authors: Iwamoto
authors: Mami
authors: M
authors: Tamai
authors: Kazuhiko
authors: K
authors: Arima
authors: Tomoki
authors: T
authors: Origuchi
authors: Hideki
authors: H
authors: Nakamura
authors: Makoto
authors: M
authors: Osaki
authors: Toshiyuki
authors: T
authors: Tsurumoto
authors: Hiroyuki
authors: H
authors: Shindo
authors: Katsumi
authors: K
authors: Eguchi
authors: Atsushi
authors: A
authors: Kawakami
mesh_terms: D001172:Arthritis, Rheumatoid / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D020868:Gene Silencing; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000037:antagonists & inhibitors / Q000378:metabolism; D012260:Ribonucleases; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D015850:Interleukin-6; D008070:Lipopolysaccharides; D034741:RNA, Small Interfering; D019947:Receptors, Interleukin-6; D050796:STAT3 Transcription Factor; D014157:Transcription Factors; D012260:Ribonucleases; C510646:ZC3H12A protein, human