MAPK-dependent regulation of IL-1-and β-adrenoreceptor-induced inflammatory cytokine production from mast cells: Implications for the stress response

David S. Chi, S. Matthew Fitzgerald, Shannon Pitts, Karen Cantor, Ellis King, Steve A. Lee, Shau Ku Huang, Guha Krishnaswamy

研究成果: 雜誌貢獻文章同行評審

31 引文 斯高帕斯(Scopus)

摘要

Background: Catecholamines, such as epinephrine, are elaborated in stress responses, and mediate vasoconstriction to cause elevation in systemic vascular resistance and blood pressure. Our previous study has shown that IL-1 can induce mast cells to produce proinflammatory cytokines which are involved in atherogenesis. The aim of this study was to determine the effects of epinephrine on IL-1-induced proatherogenic cytokine production from mast cells. Results: Two ml of HMC-1 (0.75 × 106 cells/ml) were cultured with epinephrine (1 × 10-5 M) in the presence or absence of IL-1β (10 ng/ml) for 24 hrs. HMC-1 cultured alone produced none to trace amounts of IL-6, IL-8, and IL-13. IL-1β significantly induced production of these cytokines in HMC-1, while epinephrine alone did not. However, IL-6, IL-8, and IL-13 production induced by IL-1β were significantly enhanced by addition of epinephrine. The enhancing effect appears to involve NF-κB and p38 MAPK pathways. Flow cytometry showed the presence of β1 and β2 adrenoreceptors on resting mast cells. The enhancing effect of proatherogenic cytokine production by epinephrine was down regulated by the β1 and β2 adrenoceptor antagonist, propranolol, but not by the β1 adrenoceptor antagonist, atenolol, suggesting the effect involved β2 adrenoceptors. The enhancing effect of epinephrine on proatherogenic cytokine production was also down regulated by the immunosuppressive drug, dexamethasone. Conclusions: These results not only confirm that an acute phase cytokine, IL-1β, regulates mast cell function, but also show that epinephrine up regulates the IL-1β induction of proatherogenic cytokines in mast cells. These data provide a novel role for epinephrine, a stress hormone, in inflammation and atherogenesis.

原文英語
文章編號22
期刊BMC Immunology
5
DOIs
出版狀態已發佈 - 9月 21 2004
對外發佈

ASJC Scopus subject areas

  • 免疫學

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