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Serotonin 5‐HT2A receptor activation potently inhibits TNF‐α mediated inflammation in vivo, and blocks the development of asthma
Author(s) -
Nau Felix Joseph,
Yu Banging,
Miller Justin,
Ahlert Terry,
Cormier Stephania,
Nichols Charles D.
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1120.1
Subject(s) - proinflammatory cytokine , inflammation , receptor , agonist , receptor antagonist , allergic inflammation , 5 ht receptor , serotonin , pharmacology , immunology , medicine , antagonist
Here, we show that activation of serotonin 5‐HT2A receptors has potent anti‐inflammatory effects in whole animal models of inflammation. Systemic administration of the 5‐HT2A agonist, R‐DOI, potently inhibits the inflammatory effects of TNF‐α mediated inflammation and decreases expression of key proinflammatory markers like ICAM1, CCL5, MCP1, as well as circulating levels IL6. These effects are potent in vascular tissues like the aortic arch, and superpotent in the gut, where R‐DOI doses as low as 0.01 mg/kg completely blocked the proinflammatory effects of TNF‐α. Importantly, pre‐administration of the 5‐HT2A selective antagonist, M100907, blocked the anti‐inflammatory effects of DOI. Next, we examined the effects of 5‐HT2A receptor activation on a common human inflammatory disease, allergic asthma. We found that in a mouse model of allergic asthma, 5‐HT2A receptor activation completely and potently blocked the development of airways hyper‐responsiveness, eosinophilia, inflammation, and mucus overproduction. Taken together, our results have defined a novel role for serotonin and 5‐HT2A receptors in inflammatory processes, and suggest that activation of 5‐HT2A receptors represent a novel therapeutic strategy for treating chronic human inflammatory diseases. Supported by: NIH R21HL095961.