We examined the possible role of hydrogen sulfide (H2S) in the pathogenesis of oleic acid (OA)-induced acute lung injury (ALI) and its regulatory effects on the inflammatory response. Compared to control rats, the OA-treated rats had decreased partial pressure of oxygen in the arterial blood (PaO2) levels, an increased pulmonary wet/dry weight (W/D) ratio, increased index of quantitative assessment (IQA) score and increased frequency of polymorphonuclear (PMN) cells in the lung 2, 4 or 6 h after OA injection (0.1 ml/kg, intravenous injection). In addition, significantly increased IL-6, IL-8 and IL-10 levels together with decreased H2S levels were observed in the plasma and lung tissue of OA-treated rats compared to controls. Administration of the H2S donor sodium hydrosulfide (NaHS, 56 μmol/L, intraperitoneal injection) into OA-treated rats increased the PaO2 level, reduced the lung W/D ratio and infiltration of PMN cells, and alleviated the degree of ALI (measured by the IQA score). In addition, NaHS decreased IL-6 and IL-8 levels but increased IL-10 levels in the plasma and lung tissues, suggesting that H2S may regulate the inflammatory response during ALI via regulation of IL-6, IL-8 and IL-10. Thus, the down-regulation of endogenous H2S production might be involved in the pathogenesis of OA-induced ALI in rats.
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References
1.
Milberg JA, Davis DR, Steinberg KP, Hudson LD. Improved survival of patients with acute respiratory distress syndrome (ARDS). JAMA273:306–309, 1995.
2.
Luhr OR, Antonsen K, Karlsson M, Aardal S, Thorsteinsson P, Frostell CG, Bonde J, the ARF Study Group. Incidence and mortality after acute respiratory failure and acute respiratory distress syndrome in Sweden, Denmark and Iceland. Am J Respir Crit Care Med159:1849–1861, 1999.
3.
Rubenfeld GD, Caldwell E, Peabody E, Weaver J, Martin DP, Neff M, Stern EJ, Hudson LD. Incidence and outcomes of acute lung injury. N Engl J Med353:1685–1693, 2005.
4.
Davidson TA, Caldwell ES, Curtis JR, Hudson LD, Steinberg KP. Reduced quality of life in survivors of acute respiratory distress syndrome compared with critically ill control patients. JAMA281:354–360, 1999.
5.
Li HX, Zhang JS, Zhao YL, Hao HJ. Effects of interleukin-10 on expression of inflammatory mediators and anti-inflammatory mediators during acute lung injury in rats. Chin Crit Care Med17:338–341, 2005.
6.
Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F II, Park DR, Pugin J, Skerrett SJ, Hudson LD, Martin TR. Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med164:1896–1903, 2001.
7.
Jorens PG, Van Damme J, De Backer W, Bossaert L, De Jongh RF, Herman AG, Rampart M. Interleukin 8 (IL-8) in the bronchoalveolar lavage fluid from patients with the adult respiratory distress syndrome (ARDS) and patients at risk for ARDS. Cytokine4(6):592–597, 1992.
8.
Mukhopadhyay S, Hoidal JR, Mukheriee TK. Role of TNF alpha in pulmonary pathophysiology. Respir Res7:125, 2006.
9.
Tang CS, Li XH, Du JB. Hydrogen sulfide as a new endogenous gaseous transmitter in the cardiovascular system. Curr Vasc Pharmacol4:17–22, 2006.
10.
Zhang CY, Du JB, Bu DF, Yan H, Tang XY, Tang CS. The regulatory effect of hydrogen sulfide on hypoxic pulmonary hypertension in rats. Biochem Biophy Res Commun302:810–816, 2003.
11.
Du JB, Yan H, Tang CS. Endogenous H2S is involved in the development of spontaneous hypertension. J Peking Univ Health Sci35:102, 2003.
12.
Geng B, Chang L, Pan CS, Qi YF, Zhao J, Pang YZ, Du JB, Tang CS. Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol. Biochem Biophy Res Commun318:756–763, 2004.
13.
Zhong G, Chen F, Cheng Y, Tang CS, Du JB. The role of hydrogen sulfide in the pathogenesis of hypertension in rats induced by inhibition of nitric oxide synthase. J Hypertens21:1879–1885, 2003.
14.
Mok YY, Atan MS, Yoke Ping C, Zhong Jing W, Bhatia M, Moochhala S, Moore PK. Role of hydrogen sulphide in haemorrhagic shock in the rat: protective effect of inhibitors of hydrogen sulphide biosynthesis. Br J Pharmacol143:881–889, 2004.
15.
Kimura Y, Kimura H. Hydrogen sulfide protects neurons from oxidative stress. FASEB J18:1165–1167, 2004.
16.
Fiorucci S, Antonelli E, Distrutti E, Rizzo G, Mencarelli A, Orlandi S, Zanardo R, Renga B, Di Sante M, Morelli A. Inhibition of hydrogen sulfide generation contributes to gastric injury caused by anti-inflammatory nonsteroidal drugs. Gastroenterology129:1210–1224, 2005.
17.
Zhang H, Zhi L, Moochhala S, Moore P K, Bhatia M. Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture-induced sepsis in mice by upregulating the production of cytokines and chemokines via NF-kappaB. Am J Physiol Lung Cell Mol Physiol292: L960–971, 2007.
18.
Davidson KG, Bersten AD, Barr HA, Dowling KD, Nicholas TE, Doyle IR. Lung function, permeability, and surfactant composition in oleic acid-induced acute lung injury in rats. Am J Physiol279:L1091–L1102, 2000.
19.
Grotjohan HP, van der Heijde RM, Jansen JR, Wagenvoort CA, Versprille A. A stable model of respiratory distress by small injections of oleic acid in pigs. Intensive Care Med22:336–344, 1996.
20.
McGuigan CRM, Mullenix CP, Norlund MLL, Ward MD, Walts MM, Azarow LK. Acute lung injury using oleic acid in the laboratory rat: Establishment of a working model and evidence against free radicals in the acute phase. Curr Surg60:412–417, 2003.
21.
Steinberg KP, Milberg JA, Martin TR, Maunder RJ, Cockrill BA, Hudson LD. Evolution of bronchoalveolar cell populations in the adult respiratory distress syndrome. Am J Respir Crit Care Med150:113–122, 1994.
22.
Szapiel SV, Elson NA, Fulmer JD, Hunninghake GW, Crystal RG. Bleomycin-induced interstitial pulmonary disease in the nude, athymic mouse. Am Rev Respir Dis120:893–899, 1979.
23.
Geng B, Cui Y, Zhao J, Yu F, Zhu Y, Xu G, Zhang Z, Tang C, Du J. Hydrogen sulfide downregulates the aortic L-arginine/nitric oxide pathway in rats. Am J Physiol Regul Integr Comp Physiol293(4): R1608–1618, 2007.
24.
Tao J, Yang TD, Chen XR, Huang H. Changes in liquid clearance of alveolar epithelium after oleic acid-induced acute lung injury in rats. Chin J Traumatol7:122–126, 2004.
25.
Schuster DP. ARDS: clinical lessons from the oleic acid model of acute lung injury. Am J Respir Crit Care Med149:245–260, 1994.
26.
Connelly L, Palacios-Callender M, Ameixa C, Moncada S, Hobbs AJ. Biphasic regulation of NF-kB activity underlies the pro- and anti-inflammatory actions of nitric oxide. J Immunol166:3873–3881, 2001.
27.
Arias-Diaz J, Villa N, Hernandez J, Vara E, Balibrea JL. Carbon monoxide contributes to the cytokine-induced inhibition of surfactant synthesis by human type II pneumocytes. Arch Surg132:1352–1361, 1997.
28.
Morisaki H, Katayama T, Kotake Y, Handa M, Ikeda Y, Takeda J, Ito M, Suematsu M. Carbon monoxide modulates endotoxin-induced microvascular leukocyte adhesion through platelet-dependent mechanisms. Anesthesiology97:701–709, 2002.
29.
Doeller JE, Isbell TS, Benavides G, Koenitzer J, Patel H, Patel RP, Lancaster JR. Polarographic measurement of hydrogen sulfide production and consumption by mammalian tissues. Anal Biochem341:40–51, 2005.
30.
Mariggio MA, Pettini F, Fumarulo R. Sulfide influence on polymorphonuclear functions: a possible role for Ca2+involvement. Immunopharmacol Immunotoxicol19:393–404, 1997.
31.
Zanardo RC, Brancaleone V, Distrutti E, Fiorucci S, Cirino G, Wallace JL. Hydrogen sulfide is an endogenous modulator of leukocyte-mediated inflammation. FASEB J20:2118–2120, 2006.
32.
Rinaldi L, Gobbi G, Pambianco M, Micheloni C, Mirandola P, Vitale M. Hydrogen sulfide prevents apoptosis of human PMN via inhibition of p38 and caspase-3. Lab Invest86:391–397, 2006.
33.
Cohen J. The immunopathogenesis of sepsis. Nature420:885–891, 2002.
34.
Bhatia M, Brady M, Shokuhi S, Christmas S, Neoptolemos JP, Slavin J. Inflammatory mediators in acute pancreatitis. J Pathol190:117–125, 2000.
35.
Bhatia M, Neoptolemos JP, Slavin J. Inflammatory mediators as therapeutic targets in acute pancreatitis. Curr Opin Invest Drugs2:496–501, 2001.
36.
Bhatia M. Novel therapeutic targets for acute pancreatitis and associated multiple organ dysfunction syndrome. Curr Drug Targets Infl Allergy1:343–351, 2002.
37.
Remick D, Bolgos GR, Siddiqui J, Shin J, Nemzek JA. Six at six: interleukin-6 measured 6 h after the initiation of sepsis predicts mortality over 3 days. Shock17:463–467, 2002.
38.
Leser HG, Gross V, Scheibenbogen C, Heinisch A, Salm R, Lausen M, RuckauerK. Elevation of serum interleukin-6 concentration precedes acute phase response and reflects severity in acute pancreatitis. Gastroenterology101:782–785, 1991.
39.
Nijsten NWN, Hack CE, Helle M, ten Duis HJ, Klassen HJ, Aarden LA. Interleukin-6 and its relation to the humoral immune response and clinical response in burnt patients. Surgery109:761–767, 1991.
40.
Geiger T, Andus T, Klapproth J, Hirano T, Kishimoto T, Heinrich PC. Induction of rat acute phase proteins by interleukin-6 in vivo. Eur J Immunol18:717–721, 1988.
41.
Castell JV, Gomez-Lechon MJ, David M, Andus T, Geiger T, Trullenque R, Fabra R, Heinrich PC. Interleukin-6 is the major regulator of the acute phase protein synthesis in adult human hepatocytes. FEBS Lett24:2237–2239, 1989.
42.
Hack CE, Hart M, van Schijndel RJ, Eerenberg AJ, Nuijens JH, Thijs LG, Aarden LA. Interleukin-8 in sepsis: relation to shock and inflammatory mediators. Infect Immun60:2835–2842, 1992.
43.
Rau B, Steinbach G, Gansauge F, Mayer JM, Grunert A, Beger HG. The potential role of procalcitonin and interleukin-8 in the prediction of infected necrosis in acute pancreatitis. Gut41:832–840, 1997.
44.
Shokuhi S, Bhatia M, Christmas S, Sutton R, Neoptolemos JP, Slavin J. Levels of the chemokines growth-related oncogene alpha and epithelial neutrophil-activating protein 78 are raised in patients with severe acute pancreatitis. Br J Surg89:566–572, 2002.
45.
Kasama T, Strieter RM, Lukacs NW, Burdick MD, Kunkel SL. Regulation of neutrophil-derived chemokine expression by IL-10. J Immunol152:3559–3569, 1994.
46.
Fiorentino DF, Zlotnik A, Mosmann TR, Howard M, O’Garra A. IL-10 inhibits cytokine production by activated macrophages. J Immunol147:3815–3822, 1991.
47.
Armstrong L, Milla AB. Relative production of tumour necrosis factor alpha and interleukin-10 in adult respiratory distress syndrome. Thorax52:442–446, 1997.
48.
Howard M, O’Garra A, Ishida H, Malefyt RD, Devries J. Biological properties of interleukin-10. J Clin Immunol12:239–247, 1992.
49.
Howard M, Muchamuel T, Andrade S, Menon S. Interleukin-10 protects mice from lethal endotoxemia. J Exp Med177:1205–1208, 1993.
50.
Smith SR, Terminelli C, Kenworthy-Bott L, Calzetta A, Donkin J. The cooperative effects of TNF-alpha and IFN-gamma are determining factors in the ability of IL-10 to protect mice from lethal endotoxemia. J Leuk Biol55:711–718, 1994.
51.
van der Poll T, Smith SR, Swanson SW, Hack CE, Lowry SF, Moldawer LL. Effects of IL-10 on systemic inflammatory response during lethal primate endotoxemia. J Immunol158:1971–1975, 1997.
52.
Goodman RB, Pugin J, Lee JS. Cytokine-mediated inflammation in acute lung injury. Cytok Growth Factor Rev14:523–535, 2003.
53.
Zhang H, Zhi L, Shabbir MM, Moore PK, Madhav B. Hydrogen sulfide acts as an inflammatory mediator in cecal ligation and puncture-induced sepsis in mice by upregulating the production of cytokines and chemokines via NF-kappaB. Am J Physiol Lung Cell Mol Physiol292: L960–L971, 2007.
