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 microM and 1.3 +/- 0.6 microM respectively and these activities were blocked by the H1 selective antagonist mepyramine. Histamine (EC50 = 1.8 +/- 1.1 microM) 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.


CONCLUSIONS
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.
Wang
S L
SL
Department of Molecular Biology, Neurocrine Biosciences, Inc, 12790 El Camino Real, San Diego, CA 92130, USA. swang@neurocrine.com
Malany
S
S
Wang
Q
Q
Santos
M A
MA
Crowe
P D
PD
Maki
R A
RA
D045744:Cell Line, Tumor; D002927:Cimetidine / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism*; D008301:Maleimides / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011969:Receptors, Histamine H1 / Q000187:drug effects* / Q000378:metabolism; D013584:Sarcoma, Synovial
D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D007211:Indoles; D015850:Interleukin-6; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D011969:Receptors, Histamine H1; D002927:Cimetidine; D006632:Histamine; D011493:Protein Kinase C; C070515:bisindolylmaleimide I