| Abstract | 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. 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. |
| Authors | S L Wang, S Malany, Q Wang, M A Santos, P D Crowe, R A Maki
(Affiliation: Department of Molecular Biology, Neurocrine Biosciences, Inc, 12790 El Camino Real, San Diego, CA 92130, USA. swang at neurocrine.com)
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| Journal | Inflammation research : official journal of the European Histamine Research Society ... [et al.]
(Inflamm Res)
Vol. 55
Issue 9
Pg. 393-8
(Sep 2006)
ISSN: 1023-3830 Switzerland |
| PMID | 17122961
(Publication Type: Journal Article)
|
| Chemical References |
- Histamine H1 Antagonists
- Histamine H2 Antagonists
- Indoles
- Interleukin-6
- Maleimides
- Protein Kinase Inhibitors
- Receptors, Histamine H1
- bisindolylmaleimide I
- Histamine
- Cimetidine
- Protein Kinase C
|
| Topics |
- Cell Line, Tumor
- Cimetidine
(pharmacology)
- Histamine
(pharmacology)
- Histamine H1 Antagonists
(pharmacology)
- Histamine H2 Antagonists
(metabolism, pharmacology)
- Humans
- Indoles
(pharmacology)
- Interleukin-6
(metabolism)
- Maleimides
(pharmacology)
- Protein Kinase C
(antagonists & inhibitors, metabolism)
- Protein Kinase Inhibitors
(pharmacology)
- Receptors, Histamine H1
(drug effects, metabolism)
- Sarcoma, Synovial
|
