Article Text

Download PDFPDF

THU0091 Il-8 production induced by protein i/ii, a modulin from oral streptococci, in synoviocytes from rheumatoid arthritis (ra) patients involves the mapks and fak signalling pathways and nf-kb
  1. L Neff1,
  2. M Zeisel1,
  3. FX Limbach2,
  4. JP Klein1,
  5. D Wachsmann1,
  6. J Sibilia2
  1. 1Pharmacology
  2. 2Rheumatology, CHU Hautepierre, Strasbourg, France


Background Protein I/II, an adhesin from viridans streptococci, commensal bacteria of the oral cavity, can stimulate different cells including endothelial cells. After binding to its receptor, integrin Α5Β1, protein I/II promotes release of IL-6 and IL-8 from endothelial cells, which contributes to the recruitment of circulating leukocytes from the blood into tissues. IL-8 has recently by associated with the pathogenesis of various chronic inflammatory disorders such as RA. IL-8 could be produced in response to commensal bacteria which could disseminate through bacteremia.

Objectives To study the interactions of protein I/II with fibroblast-like synoviocytes from RA patients.


  • Protein I/II increased the IL-8 synthesis of fibroblast-like synoviocytes through transcriptional up-regulation of the IL-8 gene (ELISA and RT-PCR).

  • IL-8 synthesis was inhibited by the tyrosine kinase inhibitor herbimycin A and by inhibitors of MAPKs such as apigenin and PD 98059, while focal adhesion kinase (FAK) and ERK1/2 phosphorylation was increased by Protein I/II.

  • Protein I/II increased activated nuclear translocation of the transcription factor NF-ΚB (EMSA with an NF-ΚB specific probe). This was confirmed by inhibition with curcumin, an inhibitor of NF-ΚB, which blocked IL-8 release from protein I/II-activated synoviocytes.


  • After binding to synoviocytes, protein I/II induces IL-8 release by activaing the FAK and MAPKs signalling pathways.

  • The transcription factor NF-ΚB plays a major role in the up-regulation of IL-8 synthesis and release mediated by NF-ΚB.

  • Synoviocytes activation could be triggered by commensal bacteria, which could spread to the joints through bacteremia in RA and others forms of arthritis.

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.