Role of p38 mitogen-activated protein kinase in cardiac myocyte secretion of the inflammatory cytokine TNF-α

Cherry Ballard-Croft, D. Jean White, David L. Maass, Dixie Peters Hybki, Jureta W. Horton

Research output: Contribution to journalArticlepeer-review

71 Scopus citations

Abstract

This study examined the hypothesis that burn trauma promotes cardiac myocyte secretion of inflammatory cytokines such as tumor necrosis factor (TNF)-α and produces cardiac contractile dysfunction via the p38 mitogen-activated protein kinase (MAPK) pathway. Sprague-Dawley rats were divided into four groups: 1) sham burn rats given anesthesia alone, 2) sham burn rats given the p38 MAPK inhibitor SB203580 (6 mg/kg po, 15 min; 6- and 22-h postburn), 3) rats given third-degree burns over 40% total body surface area and treated with vehicle (1 ml of saline) plus lactated Ringer solution for resuscitation (4 ml·kg-1·percent burn-1), and 4) burn rats given injury and fluid resuscitation plus SB203580. Rats from each group were killed at several times postburn to examine p38 MAPK activity (by Western blot analysis or in vitro kinase assay); myocardial function and myocyte secretion of TNF-α were examined at 24-h postburn. These studies showed significant activation of p38 MAPK at 1-, 2-, and 4-h postburn compared with time-matched shams. Burn trauma impaired cardiac mechanical performance and promoted myocyte secretion of TNF-α. SB203580 inhibited p38 MAPK activity, reduced myocyte secretion of TNF-α, and prevented burn-mediated cardiac deficits. These data suggest p38 MAPK activation is one aspect of the signaling cascade that culminates in postburn secretion of TNF-α and contributes to postburn cardiac dysfunction.

Original languageEnglish
Pages (from-to)H1970-H1981
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume280
Issue number5 49-5
DOIs
StatePublished - May 2001

Keywords

  • Cardiac contraction-relaxation
  • Langendorff perfusion
  • Rat model of burn trauma
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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