title: Histamine induces Toll-like receptor 2 and 4 expression in endothelial cells and enhances sensitivity to Gram-positive and Gram-negative bacterial cell wall components.
abstract: Histamine is a major inflammatory molecule released from the mast cell, and is known to activate endothelial cells. However, its ability to modulate endothelial responses to bacterial products has not been evaluated. In this study we determined the ability of histamine to modulate inflammatory responses of endothelial cells to Gram-negative and Gram-positive bacterial cell wall components and assessed the role of Toll-like receptors (TLR) 2 and 4 in the co-operation between histamine and bacterial pathogens. Human umbilical vein endothelial cells (HUVEC) were incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or peptidoglycan (PGN) in the presence or absence of histamine, and the expression and release of interleukin-6 (IL-6), and NF-kappaB translocation were determined. The effect of histamine on the expression of mRNA and proteins for TLR2 and TLR4 was also evaluated. Incubation of HUVEC with LPS, LTA and PGN resulted in marked enhancement of IL-6 mRNA expression and IL-6 secretion. Histamine alone markedly enhanced IL-6 mRNA expression in HUVEC, but it did not stimulate proportional IL-6 release. When HUVEC were incubated with LPS, LTA, or PGN in the presence of histamine marked amplification of both IL-6 production and mRNA expression was noted. HUVEC constitutively expressed TLR2 and TLR4 mRNA and proteins, and these were further enhanced by histamine. The expression of mRNAs encoding MD-2 and MyD88, the accessory molecules associated with TLR signalling, were unchanged by histamine treatment. These results demonstrate that histamine up-regulates the expression of TLR2 and TLR4 and amplifies endothelial cell inflammatory responses to Gram-negative and Gram-positive bacterial components.
authors.affiliation: Division of Allergy, Clinical Immunology, and Rheumatology, Department of Medicine, The University of Kansas Medical Center, Kansas City, KS, USA. jtalreja@kumc.edu
authors.forename: Jaya
authors.initials: J
authors.lastname: Talreja
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Kabir
authors.forename: Michael
authors.initials: M
authors.lastname: B  Filla
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Stechschulte
authors.forename: Kottarappat N
authors.initials: KN
authors.lastname: Dileepan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation / Q000032:analysis; D000954:Antigens, Surface / Q000032:analysis; D001419:Bacteria / Q000276:immunology*; D002473:Cell Wall / Q000276:immunology; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000276:immunology*; D006632:Histamine / Q000276:immunology*; D006634:Histamine H1 Antagonists / Q000276:immunology; D006801:Humans; D015850:Interleukin-6 / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology; D051218:Lymphocyte Antigen 96; D008562:Membrane Glycoproteins / Q000032:analysis / Q000276:immunology*; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B / Q000276:immunology; D010457:Peptidoglycan / Q000276:immunology; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis / Q000276:immunology*; D011971:Receptors, Immunologic / Q000032:analysis; D013682:Teichoic Acids / Q000276:immunology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D015854:Up-Regulation / Q000276:immunology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D006634:Histamine H1 Antagonists; D015850:Interleukin-6; C495377:LY96 protein, human; D008070:Lipopolysaccharides; D051218:Lymphocyte Antigen 96; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D010457:Peptidoglycan; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D013682:Teichoic Acids; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; C009900:lipoteichoic acid; D006632:Histamine