Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia

Hiroshi Saito, Cam Patterson, Zhaoyong Hu, Marschall S. Runge, Ulka Tipnis, Mala Sinha, John Papaconstantinou

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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-1β and tumor necrosis factor (TNF)-α, occurred rapidly before the induction of IL-6 mRNA and protein. Although stimulation of isolated rat neonatal myocardial cells with IL-1β or TNF-α induced IL-6 mRNA in vitro, nonmyocardial heart cells produced higher levels of IL-6 mRNA upon stimulation with IL-1β. In situ hybridization and immunohistochemical analyses localized the IL-6 expression primarily in nomnyocardial cells in vivo. Endotoxin-induced expression of cardiac IL-1β, TNF-α, and intercellular adhesion molecule I was augmented in IL-6-deficient mice compared with control mice. Thus cardiac IL-6, expressed mainly by nonmyocardial cells via IL-1β action during endotoxemia, is likely to suppress expression of proinfiammatory mediators and to regulate itself via a negative feedback mechanism.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume279
Issue number5 48-5
StatePublished - 2000

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Endotoxemia
Interleukin-6
Interleukin-1
Messenger RNA
Tumor Necrosis Factor-alpha
Endotoxins
Cell Adhesion Molecules
Intraperitoneal Injections
Inbred C57BL Mouse
In Situ Hybridization
Lipopolysaccharides
Cytokines

Keywords

  • Cytokines
  • Heart
  • Inflammation
  • Interleukin 6-knockout mice
  • Sepsis

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia. / Saito, Hiroshi; Patterson, Cam; Hu, Zhaoyong; Runge, Marschall S.; Tipnis, Ulka; Sinha, Mala; Papaconstantinou, John.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 279, No. 5 48-5, 2000.

Research output: Contribution to journalArticle

Saito, Hiroshi ; Patterson, Cam ; Hu, Zhaoyong ; Runge, Marschall S. ; Tipnis, Ulka ; Sinha, Mala ; Papaconstantinou, John. / Expression and self-regulatory function of cardiac interleukin-6 during endotoxemia. In: American Journal of Physiology - Heart and Circulatory Physiology. 2000 ; Vol. 279, No. 5 48-5.
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