Interleukins, inducible nitric-oxide synthase

Gardner, C.R. et al., Reduced hepatotoxicity of acetaminophen in mice lacking inducible nitric oxide synthase potential role of tumor necrosis factor-alpha and interleukin-10, Toxicol. Appl. Pharmacol., 184, 27, 2002. 

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. 

Smith, J.R., Hart, P.H., Coster, D.J., Williams, K.A. Mice deficient in tumor necrosis factor receptors p55 and p75, interleukin-4, or inducible nitric oxide synthase are susceptible to endotoxin-induced uveitis, Invest. Ophthalmol. Vis. Sci. 1998, 39, 658-661. 

SPLA2, secretory phospholipase A2 COX-2, inducible nitric oxide synthase iNOS, inducible nitric oxide synthase SOD, superoxide dismutase ICAM-1, intracellular adhesion molecule-1 VCAM-1, vascular adhesion molecule-1 TNF-a, tumor necrosis factor-a IL, interleukin and MMP, matrix metalloproteinases. 

Fig. 8.1 A schematic diagram illustrating the involvement of NF-k I in gpl20, ROS, NO, PG, IL-1/3 and TNF-a-mediated neurotoxicity. NMDA-R, N-Methyl-D-aspartate receptor, cPLA2, cytosolic phospholipase A2 lyso-PtdCho, lysophosphatidylcholine AA, arachidonic acid cAMP, cyclic adenosine monophosphate PKA, protein kinase A TNF-a, tumor necrosis factor-a TNF-a-R, TNF-a-receptor IL-1/8, interleukin-1 /3 IL-l/i-R, IL-1/8-receptor, IL-6, interleukin-6 MARK, mitogen-activated protein kinase NO, nitric oxide PG, prostaglandins EP-R, prostaglandin receptors NF-kB, nuclear factor-icB NF-kB-RE, nuclear factor-/cB-response element I/cB, inhibitory subunit of NF-icB HIV-1, human immunodeficiency virus type 1 gpl20, HIV-1 coat glycoprotein COX-2, cyclooxygenase-2 iNOS, inducible nitric oxide synthase SPLA2, secretory phospholipase A2 SOD, superoxide dismutase MMP, matrix metalloproteinase and VCAM-1, vascular adhesion molecule-1...

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. 

Akama KT, Van Eldik LJ (2000) Beta-amyloid stimulation of inducible nitric-oxide synthase in astrocytes is interleukin-Ibeta- and tumor necrosis factor-alpha (TNFalpha)-dependent, and involves a TNFalpha receptor-associated factor- and NFkappaB-inducing kinase-dependent signaling mechanism. J Biol Chem 275 7918-7924... 

BH4 = Tetrahydrobiopterin CAM = Cytotoxic activated macrophage cNOS = Constitutive nitric oxide synthase CPR = Cytochrome P450 reductase EDRF = Endothelial-derived relaxation factor EPR = Electron paramagnetic resonance spectroscopy IL-1 = Interleukin-1 iNOS = Inducible nitric oxide synthase EPS = Lipopolysaccharide, or endotoxin NMMA = ISp-monomethyl-L-arginine NOS = Nitric oxide synthase ROS = Reactive oxygen species SOD = Superoxide dismutase TNF = Tumor necrosis factor. 

Zhao ML, Kim MO, Morgello S, Lee SC (2001) Expression of inducible nitric oxide synthase, interleukin-1 and caspase-1 in HIV-1 encephalitis. J Neuroimmunol 115 182-191. 

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. 

NF-kB regulates many genes involved in inflammation, such as inducible nitric oxide synthase (iNOS), proinflammatory cytokines, IL-1, mmor necrosis factor-alpha (TNF-a), IL-6, chemokine, IL-8, E-selectin, vascular cell adhesion molecule 1 (ICAM-1), and granulocyte-macrophage colony stimulating factor (GM-CSF) (Brennan et al., 1995 Akira and Kishimoto, 1997 Bames and Adcock, 1998 Rahman and MacNee, 1998 McClintock et al., 2002). Arroyo et al. (2000) found a dose-dependent increase in TNF-a, IL-6, and interleukin-1-beta (IL-1-beta) in SM-treated human keratinocyte cells. 

Abbreviations Con A, concanavalin A CTL, cytotoxic T lymphocytes IL, interleukin iNOS, inducible nitric oxide synthase KLH, keyhole-limpet hemocyanin LAK, lymphokine-activated killer cell NHEK, normal human epidermal keratinocyte NK, natural killer cell PFC, plaque-forming cell SRBC, sheep red blood cell TNF, tumor necrosis factor. 

Bourdi M, Masubuchi Y, Reilly TP, Amouzadeh HR, Martin JL, George JW, Shah AG, Pohl LR (2002) Protection against acetaminophen-induced liver injury and lethality by interleukin 10 role of inducible nitric oxide synthase. Hepatology 35 289-298 Bryant AE III, Dreifuss EE (1996) Valproic acid hepatic fatalities. III. U.S. experience since 1986. Neurology 46 465 69... 

Fig. 4.4 Involvement of Fas and NMDA receptors in apoptotic and necrotic cell death. Fas ligand (FasL) Fas receptor (Fas-R) IV-methyl-D-aspartate receptor (NMDA-R) phosphatidylcholine (PtdCho) cytosolic phospholipase A2 (CPLA2) arachidonic add (ARA) arginine (Arg) nitric oxide synthase (NOS) nitric oxide (NO) superoxide (O2) peroxynitrite (ONOO ) arachidonic add (ARA) lyso-phosphatidylcholine (lyso-PtdCho) platelet-activating factor (PAF) cytochrome c (Cytc) apoptosome complex with apoptosis-activating factor-1 (Apaf-1) and poly(ADP)ribose polymerase (PARP) secretory phospholipase (SPLA2) inducible nitric oxide synthase (iNOS) cyclooxygenase-2 (COX-2) matrix metalloproteinase (MMP) nuclear factor-kappa B (NF-kB) inhibitory form of nuclear factor kappa B (I-kB/NF-kB) nuclear factor xB-response element (NF-kB-RE) inhibitory subunit of NF-kB (I-kB) tumor necrosis factor-a (TNF-a) interleukin-ip (IL-ip) and interleukin-6 (IL-6)...

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