Interleukins, inducible nitric-oxide synthase inhibition

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. 

In addition to the inhibition of COX, lornoxicam shows weak inhibition of LPS-induced inducible nitric oxide synthase (iNOS IC50 65 pM) and LPS-induced interleukin-6 (IC50 54 pM), both of which could contribute to its potent anti-inflammatory and analgesic action (Berg et al., 1999). 

Berg, J., Fellier, H., Christoph, T., Grarup, J., Stimmeder, D. The analgesic NSAID lornoxicam inhibits cyclooxygenase (COX)-1/-2, inducible nitric oxide synthase (iNOS), and the formation of interleukin (IL)-6 in vitro, Inflamm. Res. 1999, 48, 369-79. 

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. 

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. 

Fig. 6.7 Interactions among exdtotoxidty, neuroinflammation, and oxidative stress following TBI. Plasma membrane (PM) Glutamate (Glu) phosphatidylcholine (PtdCho) cytosolic phospholipase A2 (CPLA2) lyso-phosphatidylchoUne (lyso-PtdCho) arachidonic acid (ARA) plateletactivating factor (PAF) secretory phospholipase A2 (SPLA2) reactive oxygen species (ROS) reactive nitrogen species (RNS) nitric oxide synthase (NOS) nuclear factor kB inhibited form (IkB/NFkB) nuclear factor KB-response element (NFkB-RE), inhibitory subunit of NFkB (IkB) tumor necrosis factor-a (TNF-a) interleukin-If (IL-lf ) interleukin-6 (IL-6) cyclooxygenase-2 (COX-2) lipoxygenase (LOX) peroxynitrite (ONOO ) inducible nitric oxide synthase (iNOS). Positive sign (+) indicates stimulation...

Interferon-y and/or interleukin-ip or a combination of INF-y and TNF-a induced nitric oxide synthase in rat type II pneumocytes in vitro the production of nitric oxide was inhibited by 2 -monomethyl-L-arginine in a dose-dependent manner (Punjabi et al. 1994). 

Curcumin Turmeric roots Suppresses the productirai of cytokines such as IFN-y, interleukins, and TNF inhibits the inducible nitric oxide synthase (iNOS) [40]... 

Cetkovic-Cvrlje, M., Sandler, S., and Eizirik, D. L. (1993). Nicotinamide and dexa-methasone inhibit interleukin-1-induced nitric oxide production by RINmSF cells without decreasing messenger ribonucleic acid expression for nitric oxide synthase. Endocrinology (Baltimore) 133, 1739-1743. 

NITRERGIC STIMULANTS mimic, or cause the production and release of nitric oxide (NO), which is an important mediator that is synthesized on demand. The actions of nitric oxide are very widespread, and imbalance is likely to be involved in a number of disease states. Nitric oxide synthase (NOS) has a widespread distribution in the body, and isoforms are recognized specifically constitutive and inducible (iNOS) forms. Both forms are cytosolic, Ca /calmodulin and NADPH-dependent, and inhibited by L-arginine derivatives. Induction of iNOS is by various inflammatory cytokines, particularly those stimulated by bacterial lipopolysaccarides, including tumour necrosis factor a. interferon 7 and interleukin 1 p. Induction of iNOS only is inhibited by GLUCOCORTICOIDS. 

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