INOS expression

Unphysiologically high levels of NO formed by iNOS expressed in tissues (e.g., liver, stomach, and lung) with chronic inflammation following infections of... 

Hamalainen M, Nieminen R, Vuorela P, Heinonen M and Moilanen E. 2007. Anti-inflammatory effects of flavonoids genistein, kaempferol, quercetin and daidzein inhibit STAT-1 and NF-kB activations whereas flavones, isorhamnetin, naringenins, and pelargonidin inhibit only NF-kB activation along with their inhibitory effect on iNOS expression and NO production in activated macrophagues. Mediators Inflamm 2007 45673. 

The latest studies show that reactive nitrogen species play even more important role in asthma development. It was found that exhaled nitrogen oxide, an indicator of eosinophilic airway inflammation, is drastically enhanced in asthmatic patients. Correspondingly, it has been shown that lung damage is characterized by the augmentation of nitrotyrosine and iNOS expression in neutrophils, eosinophils, and macrophages in the airways of asthmatic patients [266],... 

The concentrations of nitrite or nitrate in the sera of patients infected with H IV-1 are substantially raised, especially in those with low CD4 cell counts [118]. However, during HIV-1 infection, it is difficult to find out whether the NO production is attributable to virus replication or to opportunistic infections, or both. In vitro there is a substantial rise in nitrite concentrations from blood mononuclear cells and polymorphonuclear leucocytes from patients with AIDS, especially in those with neurological disorders and pulmonary disease caused by intracellular opportunistic pathogens [121]. Interestingly, the serum concentrations of nitrate are positively correlated with plasma and cell-associated viral loads, which suggests that HIV-1 may induce NO synthesis in vivo [119]. However, the results clearly show that there is a close relation between viral replication and iNOS expression or peaks of plasma nitrate in the absence of any opportunistic infections, in either in macaques or infected patients [119, 122, 123]. 

Andrographolide, thus, has different mechanisms of anti-inflammatory activity. It can inhibit the activation of NF-kB, suppress inducible nitric oxide synthase (iNOS) expression, inhibit COX-2 expression in human fibroblast cells and also prevent oxygen radical production by human. The compound is also able to modulate T-cell activation both in vitro as well as in vivo, it is evident that it could prevent initial T-cell priming by interfering with DC maturation and antigen presentation capacity. Therefore, andrographolide may have utility as a therapeutic agent for the treatment of autoimmune diseases, such as multiple sclerosis. " ... 

Chiou WF, Chen CF, Lin JJ. (2000) Mechanism of suppression of inducible nitric oxide synthase (iNOS) expression in RAW 264.7 cells by andrographolide. Br J Pharmacol 129 1553-1560. 

IDDM is a disease in which /3 cells of islets are selectively destroyed. How does a nonspecific effector molecule (nitric oxide) mediate the selective destruction of the /3 cell We propose that the specificity of cytokine interactions with the /8 cell, and the intrinsic sensitivity of the /3 cell to oxidative damage relative to other endocrine cells may impart this selective destruction. In rats the effects of lL-1 appear to be specific to the /3 cell. lL-1 induces iNOS expression and the overproduction of nitric oxide by /3 cells, but does not induce expression of iNOS or nitric oxide formation in other islet endocrine or nonendocrine cells of the... 

Camuesco D, Comalada M, Rodriguez-Cabezas ME, Nieto A, Lorente MD, Concha A, Zarzuelo A, Galvez J. 2004. The intestinal anti-inflammatory effect of quercitrin is associated with an inhibition in iNOS expression. Br J Pharmacol 143 908-918. 

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. 

Astrocytes also express adrenoreceptors (Hertz et al., 1984) (Richards et al., 1989) and their activation has been shown to play some role in inflammatory contexts. NE reduces iNOS expression and nitrate accumulation in LPS plus cytokines-stimulated rat primaiy astrocytes (Feinstein et al., 1993 Feinstein, 1998). The reduction in the nitrate accumulation is attenuated by propranolol, but not by phentolamine, an a antagonist (Feinstein et al., 1993) (Facchinetti et al., 2004). 

Karabiyikoglu M., Han H. S., Yenari M. A., and Steinberg G. K. (2003) Attenuation of nNOS and iNOS expression by mild hypothermia after focal cerebral ischemia depends on when cooling begins. J. Neurosurg. 98, 1271-1276. 

Bisphosphonates (particularly clodronate) have been shown to have anti-inflammatory effects in animal models of rheumatoid arthritis (RA), as well as in arthritis in humans. In adjuvant- and antigen-induced arthritis in rats, clodronate suppresses the inflammatory articular lesions in the inflamed joints [29], whilst in human RA, clodronate decreases the levels of interleukin (ILJ-1, tumor necrosis factor-alpha (TNFaand /1-microglobulin in the circulation [30]. In vitro, clodronate inhibits cytokine and nitric oxide (NO) release and inducible nitric oxide synthase (iNOS) expression in macrophage-like cells. 

Higenamine (= (+/—)- Annona squamosa (Annonaceae), l iNOS expression [inhibits... 

Blocks NFkB activation ((HIV-1 INT, PI3K, PK, RTK) [photosensitising red pigment] 4- iNOS expression) [blocks LPS-induced macrophage iNOS expression hepatoprotective]... 

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