Inducible nitric oxide synthase expression, inhibition

D16. De Vera, M. E Kim, Y. M., Wong, H. R Wang, Q Billiar, T. R., and Geller, D. A., Heat shock response inhibits cytokine-inducible nitric oxide synthase expression in rat hepatocytes. Hepatology 24,1238-1245 (1996). 

Tedeschi, E. et al. Green tea inhibits human inducible nitric-oxide synthase expression by down-regulating signal transducer and activator of transcription-1 alpha activation. Mol Pharmacol. 65, 111, 2004. 

Maggi, L. B.Jr., Sadeghi, H., Weigand, C., Scarim, A. L., Heitmeier, M. R., and Corbett, J. A. (2000). Anti-inflammatory actions of 15-deoxy-delta 12,14-prostaglandin J2 and troglitazone Evidence for heat shock-dependent and -independent inhibition of cytokine-induced inducible nitric oxide synthase expression. Diabetes 49, 346-355. 

Saura M, Martinez-Daimau R, Minty A, et al. Interleukin-13 inhibits inducible nitric oxide synthase expression in human mesangial cells. Biochem J 1996 313(Pt2) 641-6. 

Chen, C.C., Wang, J.K., and Lin, S.B. (1998). Antisense oligonucleotides targeting protein kinase C-alpha, -beta I, or -delta but not -eta inhibit lipopolysaccharide-induced nitric oxide synthase expression in RAW 264.7 macrophages involvement of a nuclear factor kappa B-dependent mechanism. J Immunol 161, 6206-14. 

The alkaloid erythraline (103), isolated from several Erythrina species which are used as Brazilian medicine plants for the treatment of inflammation, suppressed nitric oxide production and induction of inducible nitric oxide synthase expression in RAW264.7 cells stimulated by lipopolysaccharide. Erythraline also inhibits phosphorylation of mitogen -activated protein kinases. These results suggested that erythraline might inhibit the kinase activity of TAKl [69]. 

Jang SI, Jeong SI, Kim KJ, Yu HH, Park R, Kim HM, You YO (2003) Tanshinone IIA from Salvia miltiorrhiza inhibits inducible nitric oxide synthase expression and production of TNF-alpha, IL-lbeta and IL-6 in activated RAW 264.7 cells. Planta Med 69 1057... 

H.-l. Chen, H. Bai, M.-m. Xi, R. Liu, X.-j. Qin, X. Liang, W. Zhang, X.-d. Zhang, W.-l. Li and C.-x. Hai, Ethyl pyruvate protects rats from phosgene-induced pulmonary edema by inhibiting cyclooxygenase2 and inducible nitric oxide synthase expression, / Appl Toxicol, 2013, 33, 71-77. 

Chang, K., Lee, S.J., Cheong, I., et al. (2004). Nitric oxide suppress inducible nitric oxide synthase expression by inhibiting post-translational modification of Ikappa B. Exp. Mol. Med. 36, 311-324. 

Exposure to trichothecenes at levels that partially inhibit translation upregulates expression of many inflammatory and immune-related genes including macrophage, Thl and Th2 cytokines as well as chemokines, cyclooxygenase 2 and inducible nitric oxide synthase.1518 Contrastingly, suppressive effects of trichothecenes on leukocyte function are intimately linked with the induction of apoptosis as has been demonstrated in macrophages, T cells and B cells both in vivo and in vitro.19-20... 

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. " ... 

Corbett, J. A., and McDaniel, M. L. (1995). Intraislet release of interleukin 1 inhibits jS-cell function by inducing /3-cell expression of inducible nitric oxide synthase. J. Exp. Med. 181, 559-568. 

T5. Trachtman, H., Futterweit, S., Singhal, P. C., Franki, N., Sharma, M., Sharma, R., and Savin, V., Circulating factor in patients with recurrent focal segmental glomerulosclerosis postrenal transplantation inhibits expression of inducible nitric oxide synthase and nitric oxide production by cultured rat mesangial cells. J. Invest. Med. 47, 114 (1999). 

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. 

WONG, H.R., MENENDEZ, I.Y., Sesquiterpene lactones inhibit inducible nitric oxide synthase gene expression in cultured rat aortic smooth muscle cells., Biochem. Biophys. Res. Comm., 1999,262,375-380. 

A major signalling pathway involves activation of a protein kinase that phosphorylates inhibitor kB proteins (IkBs) that normally inhibit the function of the nuclear transcription factor NFkB. Phosphorylation of IkB by the serine/threonine-specific IkB kinases (IKKs) leads to NFkB de-inhibition, nuclear translocation and expression of pro-inflammatory proteins such as inducible cyclooxygenase (iCOX) (which generates prostaglandins), inducible nitric oxide synthase (iNOS) (which generates vasodilatory and toxic free radicalgenerating NO) and pro-inflammatory cytokines. 

Figure 8.3. Various neurotoxins induce the expression of inducible nitric oxide synthase (iNOS) via the activation of NF-kB. Nitric oxide produced from iNOS then induces the activation of guanylate cyclase (GUCY) that catalyzes the production of cGMP. Inhibition of phosphodiesterase may also increase the level of cGMP. Cyclic GMP utilizes protein kinase G (PKG) to increase the expression of GFAP. IL-IR, IL-1 receptor TLR4, toll-like receptor4 GPCR, G protein-coupled receptor TLR3, toll-like receptor 3.

Some bisbibenzyls exhibited anti-inflammatory activity through the inhibition of LPS-induced nitric oxide synthase (NOS) in RAW 264.7 macrophages. Of the 19 bisbibenzyls tested, marchantin A (812) was the most potent (ICso 1.44 //M), which might involve in the inhibition of LPS-induced iNOS mRNA expression. The presence of phenolic hydroxyls and saturation at C-7, C-8 and/or C-7VC-8 are required for the inhibition of NO production [490]. 

---