ALCAM Deficiency Alleviates LPS-Induced Acute Lung Injury by Inhibiting Inflammatory Response

We investigated the effects and underlying mechanisms of activated leukocyte adhesion molecule (ALCAM) on acute lung injury (ALI) by using lipopolysaccharide (LPS)-induced ALI animal model and LPS-induced inflammation in vitro. In LPS-stimulated mice, ALCAM deficiency relieved lung injury, which manifested as reduced pathological changes in the lung tissue, reduced pulmonary edema, and reduced vascular permeability. Furthermore, we demonstrated that ALCAM deficiency reduced the infiltration of inflammatory cells, including neutrophil, eosinophil, and macrophages; the release of inflammatory cytokines, including IL-1 beta, IL-6, TNF-alpha, and COX2; and reduced the protein level of TLR4/NF-kappa B pathway (TLR4, MyD88, p-IkB alpha, and p-NF-kappa B p65). We also demonstrated that ALCAM deficiency reduced the expression of oxidative stress-related proteins (Nrf-2, HO-1, and NQO-1) and endoplasmic reticulum stress-related proteins (CHOP, GRP78, ATF-6, and p-eIF2 alpha). In addition, in LPS-induced inflammation in vitro, ALCAM overexpression promoted inflammatory response, oxidative stress, and ER stress. We established that ALCAM deficiency can suppress the ALI process by reducing inflammatory response, oxidative stress, and endoplasmic reticulum stress.