Impact of burn injury on hepatic TGF-beta1 expression and plasma TGF-beta1 levels.

Abstract

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. 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. 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. 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.