title: Histamine-induced production of interleukin-6 and interleukin-8 by human coronary artery endothelial cells is enhanced by endotoxin and tumor necrosis factor-alpha.
abstract: In this study, we tested the synergy between histamine and LPS, and histamine and TNF-alpha, on endothelial cell production of interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemoattractant protein-1 (MCP-1). Human coronary artery endothelial cells (HCAEC) were cultured in vitro with histamine (0.1 to 1000 microM) in the presence or absence of LPS or TNF-alpha for 24 h, and the secreted IL-6, IL-8 and MCP-1 were quantified. Unactivated HCAEC produced minimal levels of IL-6, IL-8, or MCP-1. The incubation of HCAEC with histamine resulted in low level induction of IL-6 and IL-8 production, which was dose-dependent and attained a plateau at a concentration of 10 microM. On the other hand, histamine failed to induce MCP-1 production. Stimulation of HCAEC with LPS or TNF-alpha caused dose-dependent increase in cytokine production. In the presence of all stimulatory concentrations of LPS and TNF-alpha tested, histamine was shown to further enhance IL-6 and IL-8 production. The effect of histamine on endothelial cell production of cytokines was completely inhibited by the H-1 receptor antagonist, diphenhydramine, and not by the H-2 antagonist, famotidine. Electrophoretic mobility shift assays of nuclear proteins extracted from HCAEC treated with histamine and LPS, or histamine and TNF-alpha, revealed amplified translocation of NF-kappaB proteins to the nuclei. Since both LPS and TNF-alpha potentiated histamine-induced cytokine production, it is possible that these activators stimulate H-1 receptor expression and/or augment the signal transduction pathways leading to the expression of IL-6 and IL-8. These results indicate the importance of synergy between histamine and other inflammatory stimuli on endothelial cell activation and implicate their cooperative participation in vascular leak and inflammation.
authors.affiliation: Division of Allergy, Department of Medicine, Kansas City, Kansas 66160, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: L
authors.initials: L
authors.lastname: Chi
authors.forename: D J
authors.initials: DJ
authors.lastname: Stechschulte
authors.forename: K N
authors.initials: KN
authors.lastname: Dileepan
mesh_terms: D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000096:biosynthesis; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D004155:Diphenhydramine / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000276:immunology*; D015738:Famotidine / Q000494:pharmacology; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis*; D016209:Interleukin-8 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D018932:Chemokine CCL2; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D015850:Interleukin-6; D016209:Interleukin-8; D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D015738:Famotidine; D006632:Histamine; D004155:Diphenhydramine