Diethyldithiocarbamate inhibits iNOS expression in human lens epithelial cells stimulated by IFN-gamma and LPS
De-xin LI
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
Search for more papers by this authorCorresponding Author
Si-ling WANG
Correspondence to Prof Si-ling WANG. Phn 86-24-2384-3711, ext 3641. E-mail [email protected]Search for more papers by this authorYoshimasa ITO
School of Pharmacy, Kinki University, Osaka 577-8502, Japan;
Pharmaceutical Research and Technology Institute, Kinki University, Osaka 577-8502, Japan
Search for more papers by this authorJing-hai ZHANG
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
Search for more papers by this authorChun-fu WU
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
Search for more papers by this authorDe-xin LI
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
Search for more papers by this authorCorresponding Author
Si-ling WANG
Correspondence to Prof Si-ling WANG. Phn 86-24-2384-3711, ext 3641. E-mail [email protected]Search for more papers by this authorYoshimasa ITO
School of Pharmacy, Kinki University, Osaka 577-8502, Japan;
Pharmaceutical Research and Technology Institute, Kinki University, Osaka 577-8502, Japan
Search for more papers by this authorJing-hai ZHANG
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
Search for more papers by this authorChun-fu WU
Department of Pharmaceutics, College of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China;
Search for more papers by this authorAbstract
Aim: To investigate the biological activity of human lens epithelial cells (HLEC)in producing inducible nitric oxide synthase (iNOS) and nitric oxide (NO), and to assesse the effect of diethyldithiocarbamate (DDC) on iNOS mRNA levels and expression of NOS.
Methods: The human lens epithelial cell line SRA 01/04 was used in this experiment. Semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting were used to detect, respectively, iNOS mRNA expression and protein production.
Results: A costimulation by interferon gamma (IFN-γ) and lipopolysaccharide (LPS) was necessary for iNOS expression in HLEC. The expression of iNOS was significantly reduced in a dosedependent manner by adding DDC from 10 μmol/L to 1 mmol/L. Conclusion: The expression of iNOS in HLEC needs co-stimulation with IFN-γ and LPS and it is inhibited by DDC.
References
- 1 Ito Y, Nabekura T, Takeda M, Nakao M, Terao M, Hori R, et al. Nitric oxide participates in cataract development in selenite-treated rats. Curr Eye Res 2001; 22: 215–20.DOI: 10.1076/ceyr.22.3.215.5516
- 2 Moncada S, Higgs A. The L-arginine-nitric oxide pathway. N Engl J Med 1993; 329: 2002–12.DOI: 10.1056/NEJM199312303292706
- 3 Griffth OW, Stuehr DJ. Nitric oxide synthases: properties and catalytic mechanism. Annu Rev Physiol 1995; 57: 707–36.DOI: 10.1146/annurev.ph.57.030195.003423
- 4 Asano K, Chee CB, Gaston B, Lilly CM, Gerard C, Drazen JM, et al. Constitutive and inducible nitric oxide synthase gene expression, regulation, and activity in human lung epithelial cells. Proc Natl Acad Sci USA 1994; 91: 10089–93.
- 5 Fimiani C, Magazine H, Welters ID, Bilfinger TV, Salsano F, Tonnesen E, et al. Antagonism of LPS and IFN-gamma induced iNOS expression in human atrial endothelia by morphine, anandamide, and estrogen. Acta Pharmacol Sin 2000; 21: 405–9.
- 6 Salzman AL, Eaves-Pyles T, Linn SC, Denenberg AG, Szabo C. Bacterial induction of inducible nitric oxide synthase in cultured human intestinal epithelial cells. Gastroenterology 1998; 114: 93–102.
- 7 Hussaini IM, Zhang YH, Lysiak JJ, Shen TY. Dithiolane analogs of lignans inhibit interferon-gamma and lipopolysaccharide-induced nitric oxide production in macrophages. Acta Pharmacol Sin 2000; 21: 897–904.
- 8 Jacquemin E, de Kozak Y, Thillaye B, Courtois Y, Goureau O. Expression of inducible nitric oxide synthase in the eye from endotoxin-induced uveitis rats. Invest Ophthalmol Vis Sci 1996; 37: 1187–96.
- 9 Goureau O, Lepoivre M, Becquet F, Courtois Y. Differential regulation of inducible nitric oxide synthase by fibroblast growth factors and transforming growth factor γ in bovine retinal pigmented epithelial cells: inverse correlation with cellular proliferation. Proc Natl Acad Sci USA 1993; 90: 4276–80.
- 10 Ito Y, Cai H, Terao M, Tomohiro M. Preventive effect of diethyldithiocarbamate on selenite-induced opacity in cultured rat lenses. Ophthalmic Res 2001; 33: 52–9.DOI: 10.1159/000055642
- 11 Brown GC. Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1999; 1411: 351–69.
- 12 Radi R, Cassina A, Hodara R. Nitric oxide and peroxynitrite interactions with mitochondria. Biol Chem 2002; 383: 401–9.DOI: 10.1515/BC.2002.044
- 13 Moncada S, Palmer RM, Higgs EA. Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 1991; 43: 109–42.
- 14 Lorsbach RB, Murphy WJ, Lowenstein CJ, Snyder SH, Russell SW. Expression of the nitric oxide synthase gene in mouse macrophages activated for tumor cell killing. Molecular basis for the synergy between interferon-gamma and lipopolysaccharide. J Biol Chem 1993; 268: 1908–13.
- 15 Xie QW, Whisnant R, Nathan C. Promoter of the mouse gene encoding calcium-independent nitric oxide synthase confers inducibility by interferon gamma and bacterial lipopolysaccharide. J Exp Med 1993; 177: 1779–84.DOI: 10.1084/jem.177.6.1779
- 16 Lowenstein CJ, Alley EW, Raval P, Snowman AM, Snyder SH, Russell SW, et al. Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci USA 1993; 90: 9730–4.
- 17 Gao J, Morrison DC, Parmely TJ, Russell SW, Murphy WJ. An interferon- γ-activated site (GAS) is necessary for full expression of the mouse iNOS gene in response to interferon-γ and lipopolysaccharide J Biol Chem 1997; 272: 1226–30.DOI: 10.1074/jbc.272.2.1226
- 18 Weinstein SL, Sanghera JS, Lemke K, DeFranco AL, Pelech SL. Bacterial lipopolysaccharide induces tyrosine phosphorylation and activation of mitogen-activated protein kinases in macrophages. J Biol Chem 1992; 267: 14955–62.
- 19 Neary JT. MAPK cascades in cell growth and death. News Physiol Sci 1997; 12: 286–93.
- 20 Xie Q, Kashiwabara Y, Nathan C. Role of transcription factor NF-κB/Rel in induction of nitric oxide synthase. J Biol Chem 1994; 269: 4705–8.
- 21 Goldring CE, Reveneau S, Algarte M, Jeannin JF. In vivo footprinting of the mouse inducible nitric oxide synthase gene: inducible protein occupation of numerous sites including Oct and NF-IL6. Nucleic Acids Res 1996; 24: 1682–7.DOI: 10.1093/nar/24.9.1682
- 22 Kamijo R, Harada H, Matsuyama T, Bosland M, Gerecitano J, Shapiro D, et al. Requirement for transcription factor IRF-1 in NO synthase induction in macrophages. Science 1994; 263: 1612–5.
- 23 Martin E, Nathan C, Xie QW. Role of interferon regulatory factor 1 in induction of nitric oxide synthase. J Exp Med 1994; 180: 977–84.DOI: 10.1084/jem.180.3.977
- 24 de Vera ME, Shapiro RA, Nussler AK, Mudgett JS, Simmons RL, Morris SMJ, et al. Transcriptional regulation of human inducible nitric oxide synthase (NOS2) gene by cytokines: initial analysis of the human NOS2 promoter. Proc Natl Acad Sci USA 1996; 93: 1054–9.DOI: 10.1073/pnas.93.3.1054
- 25 Moellering D, McAndrew J, Jo H, Darley-Usmar VM. Effects of pyrrolidine dithiocarbamate on endothelial cells: protection against oxidative stress. Free Radic Biol Med 1999; 26: 1138–45.DOI: 10.1016/S0891-5849(98)00300-1
- 26 Schreck R, Meier B, Mannel DN, Droge W, Baeuerle PA. Dithiocarbamates as potent inhibitor of nuclear factor κB activation in intact cells. J Exp Med 1992; 175: 1181–94.DOI: 10.1084/jem.175.5.1181
- 27 Kim CH, Kim JH, Moon SJ, Hsu CY, Seo JT, Ahn YS. Biphasic effect of dithiocarbamates on the activity of nuclear factor-κB. Eur J Pharmacol 2000; 392: 133–6.DOI: 10.1016/S0014-2999(00)00109-6
