Effect of Pro-Inflammatory and Immunoregulatory Cytokines on Human Tenocytes

Tendon injury induces a local inflammatory response, characterized by the induction of pro-inflammatory cytokines. The aim of the present study was to analyze the effects of TNF alpha, IL-6 and IL-10 on key parameters of tendon homeostasis. Cultured primary human tenocytes were treated with the recombinant cytokines IL-6, IL-10, TNF alpha, or combinations of TNF alpha with IL-6 and IL-10 (10 ng/mL, 6, 24 h). Expression of type I collagen, elastin, MMP-1, TNF alpha, IL-1 beta, IL-6, IL-10, and suppressors of cytokine signaling (SOCS1, 3) was analyzed with the use of RTD-PCR, immunocytochemistry, and Western blot analysis. In response to TNF alpha, tenocytes reduced their type I collagen deposition but increased their elastin gene expression and highly upregulated their expression for MMP-1, pro-inflammatory (TNF alpha, IL-1 beta) and immunoregulatory (IL-6, IL-10) cytokines. TNF alpha stimulation augmented SOCS1, whereas SOCS3 expression in tenocytes was also induced by IL-6. The treatment of tenocytes with IL-6 and IL-10 had no effect on cytokine expression. Neither IL-6 nor IL-10 modulated the observed effects of TNF alpha significantly. These results indicate that TNF alpha strongly activates the tenocytes to amplify their own TNF alpha expression and, subsequently, that of other regulatory cytokines and matrix degrading enzymes. However, the impact of IL-6 and IL-10 on tenocytes remains unclear. (C) 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:1071-1077, 2010