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

, : MAPK-dependent regulation of IL-1- and beta-adrenoreceptor-induced inflammatory cytokine production from mast cells: implications for the stress response. Bmc Immunology 5: 22-22

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 x 10(6) cells/ml) were cultured with epinephrine (1 x 10(-5) M) in the presence or absence of IL-1 beta (10 ng/ml) for 24 hrs. HMC-1 cultured alone produced none to trace amounts of IL-6, IL-8, and IL-13. IL-1 beta 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-1 beta were significantly enhanced by addition of epinephrine. The enhancing effect appears to involve NF-kappa B and p38 MAPK pathways. Flow cytometry showed the presence of beta(1) and beta(2) adrenoreceptors on resting mast cells. The enhancing effect of proatherogenic cytokine production by epinephrine was down regulated by the 1 and 2 adrenoceptor antagonist, propranolol, but not by the beta(1) adrenoceptor antagonist, atenolol, suggesting the effect involved beta(2) 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-1 beta, regulates mast cell function, but also show that epinephrine up regulates the IL-1 beta induction of proatherogenic cytokines in mast cells. These data provide a novel role for epinephrine, a stress hormone, in inflammation and atherogenesis.


PMID: 15383152

DOI: 10.1186/1471-2172-5-22

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