Histamine induces interleukin-6 expression in the human synovial sarcoma cell line (SW982) through the H1 receptor

Methods The effect of histamine on inositol phosphate generation and interleukin-6 (IL-6) release from the synovial sarcoma cell line SW982 was investigated. Results SW982 cells express functional H₁ and H₂ receptors. The H₁ receptor antagonist ³H]-mepyramine binds to membranes from SW982 cells with high affinity and the binding was potently blocked by H₁ antagonists. Histamine potently stimulated phosphoinositide (PI) hydrolysis and Ca²⁺ mobilization with EC₅₀ of 4.0 ± 0.8 μM and 1.3 ± 0.6 μM respectively and these activities were blocked by the H₁ selective antagonist mepyramine. Histamine (EC₅₀ = 1.8 ± 1.1 μM) stimulated the release of IL-6 that was attenuated by selective H₁ antagonists. The PKC inhibitor, GF1090203X, blocked the histamine stimulated IL-6 release. The H₂ selective antagonist, cimetidine, had no significant effect on histamine-induced PI turnover, Ca²⁺ mobilization and IL-6 release. Conclusion We conclude that histamine stimulates IL-6 release from SW982 cells by binding to the H₁ receptor and this is coupled to the PI/PKC signal transduction pathway. Development of an H₁ antagonist that inhibits the release of IL-6 from synoviocytes may be beneficial for the treatment of inflammatory joint disease. Received 15 September 2005; returned for revision 12 December 2005; accepted by A. Falus 13 April 2006