Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
-
Lung contusion (LC) is a significant risk factor for the development of acute respiratory distress syndrome. Toll-like receptor 9 (TLR9) recognizes specific unmethylated CpG motifs, which are prevalent in microbial but not vertebrate genomic DNA, leading to innate and acquired immune responses. TLR9 signaling has recently been implicated as a critical component of the inflammatory response following lung injury. ⋯ Macrophages, isolated from TLR9 (-/-) mice, exhibited increased phagocytic activity at 24 h after LC compared with those isolated from WT mice. TLR9, therefore, appears to be functionally important in the development of progressive lung injury and inflammation following LC. Our findings provide a new framework for understanding the pathogenesis of lung injury and suggest blockade of TLR9 as a new therapeutic strategy for the treatment of LC-induced lung injury.
-
Intestinal ischemia-reperfusion (I/R) is associated with acute respiratory distress syndrome. Osteopontin (OPN), a glycoprotein secreted from immune-reactive cells, plays a deleterious role in various inflammatory diseases. Considering OPN as a pro-inflammatory molecule, we hypothesize that the treatment with its neutralizing antibody (anti-OPN Ab) protects mice against intestinal I/R-induced acute lung injury (ALI). ⋯ The lung inflammation measured by the levels of IL-6, IL-1β, and MIP-2 was also significantly downregulated in the anti-OPN Ab-treated mice as compared with the IgG control mice. Besides, the lung MPO and neutrophil infiltration in anti-OPN Ab-treated mice showed significant reduction as compared with the IgG control animals. In conclusion, we have demonstrated beneficial outcomes of anti-OPN Ab treatment in protecting against ALI, implicating a novel therapeutic potential in intestinal I/R.
-
Lung ischemia-reperfusion injury (LIRI) occurs in various clinical situations, such as transplantation, cardio pulmonary bypass, cardiac arrest, and major trauma, leading to significant morbidity and mortality. Despite researchers having spent years of effort to investigate the pathogenesis of pulmonary ischemic injury, the concrete cellular and molecular mechanisms are still unknown. We hypothesized that toll-like receptor (TLR) 3 signaling may play a vital role in inflammation responses, apoptosis, and pulmonary dysfunction during LIRI. ⋯ Pulmonary apoptosis was also inhibited after TLR3 knockout, as indicated by cleaved caspase-3 western blot and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. Levels of serum microRNAs (miRNAs), especially miRNA155, were decreased in the TLR3 I/R group compared with that of the WT I/R group. In conclusion, these data suggest that TLR3 signaling pathway may be a promising target for the treatment of lung I/R injury.