Role And Mechanisms Of TGF-β₁/Smads Signal Transduction Pathway In Early Inflammatory Response After Severe Thermal Injury

On account of two facts that systemic inflammatory response will occur in the early phase of severe burns and TGF-β₁/Smads signaling pathway is tightly connected with inflammatory regulation, we investigated the role in the early inflammation following a severe burn which TGF-β₁/Smads signaling played. Results showed that suppression of TGF- β1/Smads signaling with specific inhibiter(SB431542) diminished bum-induced expressions of both proinflammatory cytokines (TNFa,IL-1β,IL-6) and cell adhesion molecules (ICAM-l,E-Selectin,CD11b). whereas severe burn induced an inhibitory signal in the TGF- β1/Smads signaling pathway between 4 and 8 hours postbum, pretreatment with SB431542 enhanced this inhibitory tendency. Moreover, inhibition of TGF- β1/Smads signaling could attenuate lung injury, diminished pulmonary water contents and microvascular hyperpermeability postbum. These findings indicate Smad signaling participates in regulations of early stage inflammatory response postbum and suppression of smads signaling may be some kinds of self-modulating following bum trauma, in that way organism attenuate its inflammatory responses moderately.