title: MAPK-dependent regulation of IL-1- and beta-adrenoreceptor-induced inflammatory cytokine production from mast cells: implications for the stress response.
abstract: 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 106 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 beta1 and beta2 adrenoreceptors on resting mast cells. The enhancing effect of proatherogenic cytokine production by epinephrine was down regulated by the beta1 and beta2 adrenoceptor antagonist, propranolol, but not by the beta1 adrenoceptor antagonist, atenolol, suggesting the effect involved beta2 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.
authors.affiliation: Department of Internal Medicine, James H, Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee 37614, USA. chi@etsu.edu.
authors.forename: David S
authors.initials: DS
authors.lastname: Chi
authors.forename: S Matthew
authors.initials: SM
authors.lastname: Fitzgerald
authors.forename: Shannon
authors.initials: S
authors.lastname: Pitts
authors.forename: Karen
authors.initials: K
authors.lastname: Cantor
authors.forename: Ellis
authors.initials: E
authors.lastname: King
authors.forename: Steven A
authors.initials: SA
authors.lastname: Lee
authors.forename: Shau-Ku
authors.initials: SK
authors.lastname: Huang
authors.forename: Guha
authors.initials: G
authors.lastname: Krishnaswamy
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D001161:Arteriosclerosis / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D016207:Cytokines / Q000096:biosynthesis*; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007249:Inflammation / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology / Q000502:physiology*; D018793:Interleukin-13 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D016209:Interleukin-8 / Q000096:biosynthesis; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology*; D016328:NF-kappa B / Q000502:physiology; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D018342:Receptors, Adrenergic, beta-1 / Q000096:biosynthesis; D018343:Receptors, Adrenergic, beta-2 / Q000096:biosynthesis; D013312:Stress, Physiological / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology
chemical_list: D000319:Adrenergic beta-Antagonists; D016207:Cytokines; D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D007375:Interleukin-1; D018793:Interleukin-13; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D011943:Receptors, Adrenergic, beta; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D004837:Epinephrine