Recently we reported that HMGB1/TLR4 signaling mediates the HS-induced increase in TLR2 surface expression and decrease in TLR4 surface expression in the lung as well as in mouse lung vascular ECs (MLVEC) (122) . These alterations in TLR4 and TLR2 expression result in HMGB1-mediated activation of NAD(P)H oxidase and expression of ICAM-1 in MLVEC that is TLR4 dependent in the early phase and switches to being TLR2 dependent in the late phase following HS. More importantly, the HS-induced surface expression of TLR2 contributes to an enhanced activation of MLVEC and augmented pulmonary PMN infiltration in response to the TLR2 agonist PGN. Thus, the study demonstrates a novel mechanism underlying HS-augmented lung inflammation, namely that induction of increased TLR2 surface expression in lung endothelial cells, which is induced by HS/R and mediated by HMGB1 activation of TLR4 signaling, is an important mechanism responsible for EC-mediated inflammation and organ injury following HS (122) .