C1632 protects against LPS-induced acute lung injury by regulating AXL-mediated MAPK/NF-κB signaling pathway

Acute lung injury (ALI), a leading pulmonary inflammatory disorder, is associated with high morbidity and mortality rates. AXL, a member of the TAM family, plays a significant role in the innate immune and inflammatory responses. This study aimed to evaluate the therapeutic potential of C1632 and its mechanisms in the treatment of LPS-induced ALI/ARDS. The results demonstrated that C1632 pretreatment inhibited the transcription, expression, and secretion of LPS-induced inflammatory factors (IL-6, TNF-α) and vascular adhesion molecules (VCAM-1, ICAM-1). Furthermore, it reduced inflammatory cell infiltration in the lungs, thereby alleviating LPS-induced histopathological changes and lung injury in mice. Mechanistically, C1632 suppressed AXL transcription and expression, which inhibited the activation of the MAPK/NF-κB signaling pathway triggered by LPS stimulation. Both in vitro and in vivo studies confirmed that C1632 administration did not exhibit significant cytotoxicity. Additionally, it did not cause functional or structural damage to the liver and kidneys in mice, nor did it induce other acute toxic effects. In summary, these findings suggest that AXL is a novel target for MAPK/NF-κB signaling pathway mediated anti-inflammatory treatment and C1632 is a promising therapeutic agent for ALI/ARDS treatment.