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INFLAMMATION, CYTOKINES, AND TEMPERATURE REGULATION
1Shriners Hospitals for Children and Department of Surgery, and 2Department of Human Genetics and Biological Chemistry, University of Texas Medical Branch, Galveston, Texas 77550
Submitted 24 January 2003 ; accepted in final form 9 June 2003
Major thermal injury results in severe prolonged responses with three
components: a hypermetabolic response, inflammatory responses, and endogenous
wound-healing processes. We showed that use of liposome-mediated gene transfer
of the insulin-like growth factor I (IGF-I) reduces burn-induced inflammatory
responses and enhances wound healing. In the present study, we found transient
increased levels of IGF-I protein in rats exposed to thermal trauma via
liposomal gene transfer in an effort to define the transcriptional events that
occur after IGF-I delivery at the site of injury. The beneficial effects of
IGF-I gene transfer act partly via amelioration of burn-induced inflammatory
responses that mediate cell death through caspase-3 activity and Bax
expression. IGF-I gene transfer induces selective stimulation of activation
protein-1 DNA-binding activity and activation of antiapoptotic, but not
inflammatory, NF-
B transcription factors. Data were consistent with our
hypothesis that the beneficial effects of IGF-I gene transfer on burned rats
act in part via activation protein-1 and NF-
B transcriptional
regulation and the concordance between the results obtained with
antiapoptotic, as opposed to the proapoptotic, sequences as well as the
corresponding changes in measures of cell death via Bax and caspase-3
mechanisms.
nuclear factor-
B; thermal injury; activation protein-1; caspase-3; Bax
This article has been cited by other articles:
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T. H. Elsasser Insulin-like growth factor-I: a traffic control device on the road to tissue recovery Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2003; 285(4): R722 - R723. [Full Text] [PDF] |
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