Burn injury-induced alterations in wound inflammation and healing are associated with suppressed hypoxia inducible factor-1α expression

Martin G. Schwacha, Eike Nickel, Tanjanika Daniel

Research output: Contribution to journalArticlepeer-review

24 Scopus citations

Abstract

A major complication associated with burn injury is delayed wound healing. While healing of the burn injury site is essential, healing of distal injury sites caused by surgical interventions and other processes also is important. The impact of burn injury on healing of these distal wound sites is not understood clearly. To study this, mice were subjected to major burn injury or a sham procedure. Immediately following, excisional wounds were made on the dorsal surface caudal to the burn site and wound closure was monitored over a 7-d period by planimetry. In a second series of experiments, plasma and excisional wounds were collected for in vitro analysis of cyto- and chemokine levels, L-arginine metabolism,and hypoxia-inducible factor (HIF)-1α expression.At 1-7 d post-injury, a significant inflammatory response was evident in both groups, but the healing process was delayed in the burn-injured mice. At 3 d post-injury, wound levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and keratinocyte-derived chemokine were suppressed in the burn group. This difference in the wound inflammatory response was independent of changes in L-arginine metabolism (nitrate levels, inducible nitric oxide synthase expression, arginase activity), but correlated with a marked reduction in HIF-1α protein levels. In conclusion, these findings suggest that HIF-1α and the inflammatory response play a significant role in wound healing, and reduced levels of HIF-1α contribute to the impaired healing response post-burn.

Original languageEnglish (US)
Pages (from-to)628-633
Number of pages6
JournalMolecular Medicine
Volume14
Issue number9-10
DOIs
StatePublished - Sep 2008

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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