iNOS

iNOS is an inducible nitric oxide synthase that produces nitric oxide from L-arginine and acts as a key mediator of immune activation and inflammation^[1]. Mechanistically, inflammatory cells such as macrophages produce nitric oxide mainly through iNOS during inflammatory processes, where nitric oxide functions as an innate immune effector molecule^[2]. iNOS expression is regulated by inflammatory signaling pathways, including PKC, NF-κB, STAT3-NF-κB interaction, and PKCδ-IRF1 signaling, which connect cytokine or LPS stimulation to nitric oxide production^[2][3][4]. In disease models, dysregulated iNOS has been linked to sepsis, cancer, neurodegeneration, pain, arthritis, inflammatory bowel disease, liver fibrosis, and neurological disease models^[1][5][6][7]. Compared with nNOS and eNOS, iNOS differs by stimulus-responsive expression and high nitric oxide output, whereas nNOS mainly supports neuronal signaling and eNOS supports endothelial vascular regulation^[8]. However, iNOS is not solely pathological, because traumatic brain injury models showed worse outcomes after iNOS inhibition or iNOS gene deletion^[9]. For experimental applications, selective iNOS inhibitors remain useful tools for testing nitric oxide-dependent mechanisms, although no iNOS inhibitor is approved for human use^[1].