Alterations in the cardiac inflammatory response to burn trauma in mice lacking a functional Toll-like receptor 4 gene

Brandon Bruns, David Maass, Robert Barber, Jureta Horton, Deborah Carlson

Research output: Contribution to journalArticle

19 Scopus citations

Abstract

Our group and others have previously shown that Toll-like receptor 4 (TLR-4) inactivation prevents buminduced myocardial contractile dysfunction; however, the molecular mechanisms that are involved in this cardioprotection are not well defined. This present study examines the involvement of TLR-4 in the cardiac inflammatory response to thermal insult. C3H/HeJ (TLR-4 mutant mice) and C3H/HeN wild-type (WT) mice were subjected to either a sham burn or 40% full-thickness burn injury and were fluid resuscitated with lactated Ringer using the Parkland formula. Mice (n = 7-9 per group) were killed at 2,4, or 24 h postsham or burn, and heart tissue was harvested. Immunoblotting was performed to evaluate phosphorylated p38 mitogen-activated protein kinase (MAPK), nuclear p50, and cytoplasmic p50. Nuclear factor-KB was also characterized via electrophoretic mobility shift assay. Systemic and cardiac myocyte secretion of TNF-α, IL-iβ, IL-6, and IL-10 were measured by enzyme-linked immunosorbent assay. Burn injury in WT mice promoted myocardial inflammatory signaling that included increased expression of phosphorylated p38 MAPK, nuclear p50, and increased cardiac myocyte secretion of cytokines. Systemic cytokines were also increased in WT animals, although not to the extent of the myocardial cytokine expression. Toll-like receptor 4 inactivation resulted in an attenuation of several buminduced responses, including phosphorylation of p38 MAPK, nuclear translocation of nuclear factor-κB, and cytokine secretion. These data suggest that burn injury initiates an inflammatory response via Toll/IL-1 signaling in the heart, which contributes to cardiac injury and contractile dysfunction.

Original languageEnglish (US)
Pages (from-to)740-746
Number of pages7
JournalShock
Volume30
Issue number6
DOIs
StatePublished - Dec 2008

Keywords

  • Cardiac
  • Cytokine
  • Myocyte
  • Nuclear factor-κB
  • TNF-α
  • p38 mitogen-activated protein kinase

ASJC Scopus subject areas

  • Emergency Medicine
  • Critical Care and Intensive Care Medicine

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