VLA-4-dependent and -independent pathways in cell contact-induced proinflammatory cytokine production by synovial nurse-like cells from rheumatoid arthritis patients

Arthritis Research & Therapy

Masayuki Miyasaka¹  Takahiro Ochi²  Ryuji Suzuki³  Koichiro Takahi²  Kenrin Shi²  Tetsuya Tomita²  Eiji Umemoto¹  Toshiyuki Tanaka¹  Eiji Takeuchi⁴ 

[1]Laboratory of Molecular and Cellular Recognition, Osaka University Graduate School of Medicine, Osaka, Japan

[2]Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan

[3]Pharmacology Research Laboratories, Pharmaceutical Research Division, Takeda Chemical Industries Ltd, Osaka, Japan

[4]Department of Orthopaedic Surgery, Osaka Rousai Hospital, Osaka, Japan

关键词: transmigration;    rheumatoid arthritis;    nurse cells;    cytokine production;    cell adhesion;   

Others  :  1101429
DOI  :  10.1186/ar593

 received in 2002-06-26, accepted in 2002-07-15,  发布年份 2002

【 摘 要 】

Nurse-like stromal cell lines from the synovial tissue of patients with rheumatoid arthritis (RA-SNC) produce, on coculture with lymphocytes, large amounts of proinflammatory cytokines. In the present paper, we analyze the molecular events necessary for the induction of cytokine release from RA-SNC cells, and particularly the roles played by cell adhesion and the transmigration (also known as pseudoemperipolesis) of lymphocytes. For this purpose, the effects of various mAbs on the binding and transmigration of a human B-cell line, MC/car, were examined using a cloned RA-SNC line, RA-SNC77. To analyze the role of lymphocyte binding and transmigration on upregulated cytokine production by the RA-SNC77 cells, we used C3 exoenzyme-treated MC/car cells, which could bind to RA-SNC77 cells but could not transmigrate. Treatment with anti-CD29 or anti-CD49d mAb significantly reduced binding and transmigration of the MC/car cells. In contrast, the neutralizing anti-CD106/vascular cell adhesion molecule 1 mAb did not show any inhibitory effect. Likewise, none of the neutralizing mAbs against CD11a, CD18, CD44, CD49e, or CD54 showed significant effects. Binding of C3-treated or untreated MC/car cells to RA-SNC77 cells induced comparable levels of IL-6 and IL-8 production. In addition, the enhanced cytokine production by RA-SNC77 cells required direct lymphocyte contact via a very late antigen-4 (VLA-4)-independent adhesion pathway. These results indicate that, although both the VLA-4-dependent/vascular cell adhesion molecule 1-independent and the VLA4-independent adhesion pathways are involved in MC/car binding and subsequent transmigration, only the VLA4-independent adhesion pathway is necessary and sufficient for the enhanced proinflammatory cytokine production by RA-SNC77 cells. The transmigration process, which is dependent on Rho-GTPase, is not a prerequisite for this phenomenon.

【 授权许可】

   
2002 Takeuchi et al., licensee BioMed Central Ltd

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