title: Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia.
abstract: Interleukin (IL)-6 reportedly has negative inotropic and hypertrophic effects on the heart. Here, we describe endotoxin-induced IL-6 in the heart that has not previously been well characterized. An intraperitoneal injection of a bacterial lipopolysaccharide into C57BL/6 mice induced IL-6 mRNA in the heart more strongly than in any other tissue examined. Induction of mRNA for two proinflammatory cytokines, IL-1beta and tumor necrosis factor (TNF)-alpha, occurred rapidly before the induction of IL-6 mRNA and protein. Although stimulation of isolated rat neonatal myocardial cells with IL-1beta or TNF-alpha induced IL-6 mRNA in vitro, nonmyocardial heart cells produced higher levels of IL-6 mRNA upon stimulation with IL-1beta. In situ hybridization and immunohistochemical analyses localized the IL-6 expression primarily in nonmyocardial cells in vivo. Endotoxin-induced expression of cardiac IL-1beta, TNF-alpha, and intercellular adhesion molecule 1 was augmented in IL-6-deficient mice compared with control mice. Thus cardiac IL-6, expressed mainly by nonmyocardial cells via IL-1beta action during endotoxemia, is likely to suppress expression of proinflammatory mediators and to regulate itself via a negative feedback mechanism.
authors.affiliation: Department of Human Biological Chemistry and Genetics, University of Texas Medical Branch, Galveston, Texas 77555, USA. hsaito@utmb.edu
authors.forename: H
authors.initials: H
authors.lastname: Saito
authors.forename: C
authors.initials: C
authors.lastname: Patterson
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.forename: M S
authors.initials: MS
authors.lastname: Runge
authors.forename: U
authors.initials: U
authors.lastname: Tipnis
authors.forename: M
authors.initials: M
authors.lastname: Sinha
authors.forename: J
authors.initials: J
authors.lastname: Papaconstantinou
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D051743:CCAAT-Enhancer-Binding Protein-delta; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D005246:Feedback; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity; D012333:RNA, Messenger / Q000096:biosynthesis; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C497253:Cebpd protein, mouse; D007375:Interleukin-1; D015850:Interleukin-6; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D051743:CCAAT-Enhancer-Binding Protein-delta