INOS expression, increase

Ramaswamy K, He YX, Salafsky B. ICAM-1 and iNOS expression increased in the skin of mice after vaccination with gamma-irradiated cercariae of Schistosoma mansoni. Exp Parasitol 1997 86 118-132. 

Activation of P-ARs by isoproterenol enhances the expression of COX-2 and iNOS in a human urothelial cell line (Harmon et al., 2005). Since activation of P-adrenoreceptors leads to an increase in cAMP and a subsequent PKA activation, the authors investigated whether the increase in these inflammatory markers was due to activation of this pathway. However, this increase is independent of PKA, since PKA inhibitors did not reduce the augmentation in COX-2 and iNOS expression. 

Xiang, Y. and C. Rice. Expression of fish iNOS is increased by pro-inflammatory signals and xenobiotics. Mar. Environ. Res. 50 466-467, 2000. 

Increased cytokine production may also play a role in silica-induced autoimmune vascular disease. Adhesion molecule expression is elevated on vascular endothelial cells in response to TNF-a and IL-1. Adhesion molecules such as endothelial leukocyte adhesion molecule-1 (ELAM-1) and intercellular adhesion molecule-1 (ICAM-1) recruit inflammatory cells to specific sites on the vascular endothelium, and it has been hypothesized that vascular pathology following silica exposure may be the result of this interaction (Nowack et al., 1998). IFN-y is expressed at elevated levels by lymphocytes in silicotic thoracic lymph nodes and may be responsible for the long-lasting inducible nitric oxide synthase (iNOS) expression in these tissues (Friedetzky et al., 2002). The increase in IFN-y may also cause a shift towards a dominant Thl response, contributing to the maintenance of a chronic inflammatory state in silica-containing lymph nodes (Gam et al., 2000). 

Exposure to ROS and RNS causes posttranslational modifications in p53 that inhibit cellular growth. Increase in iNOS expression causes mutations in p53 at codons 247 and 248. These have been observed in inflamed lesions of patients that have ulcerative colitis, associated with colon cancer. In colon tumors, there is a high correlation between iNOS activity and G C to A T mutations at methylcytosine sites in p53. Similarly, increased iNOS expression was associated with mutations in p53 in stomach, brain, and breast cancers. NO and its derivatives, which cause mutations in cancer-related genes such as p53 therefore act as endogenous initiators and promoters in carcinogenesis. 

The effect of berberine in vivo has been studied in a rat model of AD concluding that intraperitoneal administration of berberine increased the spatial memory of animals by increasing ILlp and iNOS expression in hippocampus [68]. 

Inducible NOS (iNOS) expression and the resultant increased NO production are associated with atherosclerotic lesions (62). iNOS activity and gene transcription in VSMC was increased following exposure to IGF-I which was reduced by All pretreatment (63). 

Haematology DNA damage in peripheral blood mononuclear cells and total hydrophilic antioxidant capacity in the plasma from 19 TB patients and healthy tuberculin test-positive controls were evaluated by single-cell gel electrophoresis and inducible isoform Nitric Oxide Synthase (iNOS) expression measured by quantitative polymerase chain reaction (qPCR). Compared to controls, pulmonary TB patients under treatment presented with increased DNA damage and increased antioxidant capacity, which diminished during treatment. TB patients showed lower iNOS expression, but expression tended to increase during treatment [36 ]. 

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