Impact of burn injury on hepatic TGF-beta1 expression and plasma TGF-beta1 levels.
BACKGROUND
The liver plays a critical regulatory role in the acute inflammatory response to injury, although the mechanisms of this regulation are not well understood. transforming growth factor-beta1 (TGF-beta1) is induced after burn injury and may contribute to an inhibitory or fatal effect on hepatocytes. We investigated the association over time between plasma concentration of TGF-beta1, expression of TGF-beta1 m-RNA in liver tissue, and histologic analysis of liver apoptosis after burn injury.


METHODS
Male BALB/c mice were anesthetized and randomized to receive 0% (sham), moderate (approximately 25%) (M), or large (approximately 50%) (L) body surface area full-thickness contact burn, followed by resuscitation and analgesia. Animals were killed over a time course from 15 minutes to 24 hours after burn injury, and liver tissue and peripheral blood were collected. Plasma levels of TGF-beta1 (nanograms per milliliter) were measured by enzyme-linked immunosorbent assay. TGF-beta1 m-RNA was extracted from liver and measured by reverse transcription-polymerase chain reaction. Histology of liver apoptosis was examined after fixation and staining with TdT-mediated dUTP nick-end labeling (TUNEL) method.


RESULTS
The plasma concentration of TGF-beta in burn group L was significantly increased at 4 hours after burn when compared with sham and M burn groups. This rise in plasma TGF-beta1 was preceded by an increase in hepatic TGF-beta1 m-RNA expression at 30 minutes, 1, 2, and 4 hours after burn in the L group. Histologic analysis found greater hepatocyte death in the L group than in the M group at 8 hours after burn.


CONCLUSIONS
The levels of induced TGF-beta1 and TGF-beta1 m-RNA after L burn injury are higher and peak earlier than after M burn injury. Elevated TGF-beta1 may be associated with cell death in hepatocytes. The TGF-beta1 rise may be associated with hepatocyte injury and systemic response to massive burn.
Nishimura
T
T
Department of Surgery and Jaycee Burn Center, University of North Carolina, Chapel Hill 27599-7210, USA.
Nishiura
T
T
deSerres
S
S
Nakagawa
T
T
Brenner
D A
DA
Meyer
A A
AA
D000208:Acute Disease; D000818:Animals; D017209:Apoptosis; D001830:Body Surface Area; D002056:Burns / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005786:Gene Expression Regulation / Q000276:immunology*; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D015601:Injury Severity Score; D008099:Liver / Q000737:chemistry* / Q000166:cytology / Q000473:pathology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D012333:RNA, Messenger / Q000032:analysis; D011897:Random Allocation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis* / Q000097:blood* / Q000235:genetics
D012333:RNA, Messenger; D016212:Transforming Growth Factor beta