ISIR and its human homolog gene AK131315 strengthen LPS-induced inflammation and acute lung injury by promoting TAK1-dependent NF-κB and MAPK signaling

Acute lung injury (ALI), a critical complication observed in various clinical disorders, is characterized by widespread inflammation, neutrophil infiltration, and proinflammatory cytokine production. This study showed that the recently identified non-coding RNA ISIR and its human homolog gene AK131315 played a role in regulating lipopolysaccharide (LPS)-induced inflammatory responses. ISIR and AK131315 increased the production of inflammatory cytokines in LPS-stimulated macrophages, and exogenous ISIR aggravated LPS-induced lung inflammation in an animal model of ALI. Mechanistically, ISIR promoted LPS-triggered NF-κB and MAPK signaling and the transcription of proinflammatory cytokines by enhancing TAK1 activation. Furthermore, a significant correlation was observed between AK131315 expression and pulmonary infectious caused by Gram-negative bacteria, suggesting that AK131315 plays an important role in Bacterial infections. Altogether, these findings indicate that ISIR regulates LPS-induced inflammation and AK131315 is involved in the pathogenesis of Bacterial infections.