Regulatory effect of cytokine-induced neutrophil chemoattractant, epithelial neutrophil-activating peptide 78 and pyrrolidine dithiocarbamate on pulmonary neutrophil aggregation mediated by nuclear factor-κB in lipopolysaccharide-induced acute respiratory distress syndrome mice

Wang,Hongman; Zhao,Jiping; Xue,Guansheng; Wang,Junfei; Wu,Jinxiang; Wang,Donghui; Dong,Liang

doi:10.3892/etm.2016.3520

Regulatory effect of cytokine-induced neutrophil chemoattractant, epithelial neutrophil-activating peptide 78 and pyrrolidine dithiocarbamate on pulmonary neutrophil aggregation mediated by nuclear factor-κB in lipopolysaccharide-induced acute respiratory distress syndrome mice

Authors:
- Hongman Wang
- Jiping Zhao
- Guansheng Xue
- Junfei Wang
- Jinxiang Wu
- Donghui Wang
- Liang Dong
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Affiliations: Department of Pulmonary Medicine, The Third Affiliated Hospital of Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China, Department of Pulmonary Medicine, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China, Department of Thoracic Surgery, 205 Hospital of Chinese People's Liberation Army, Jinzhou, Liaoning 121001, P.R. China
Published online on: July 13, 2016 https://doi.org/10.3892/etm.2016.3520
Pages: 1785-1794

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Abstract

In the present study, the regulatory effect of cytokine-induced neutrophil chemoattractant (CINC) and epithelial neutrophil-activating peptide 78 (ENA-78) on pulmonary neutrophil (PMN) accumulation in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice, and the therapeutic effect of pyrrolidine dithiocarbamate (PDTC), was investigated. BALB/c mice were divided into control, LPS and PDTC + LPS groups using a random number table. The phosphorylation of nuclear factor‑κB (NF‑κB) was detected using a western blot, and the mRNA expression levels of CINC were evaluated using reverse transcription-quantitative polymerase chain reaction. The expression of NF‑κB, CINC and ENA-78 was detected using immunohistochemistry. The production of interleukin (IL)‑8 and IL‑10 in serum and broncho-alveolar lavage fluid (BALF) was analyzed using an enzyme‑linked immunosorbent assay. The total number of leukocytes and proportion of PMNs in BALF was also determined. Following injection with LPS (20 mg/kg), the expression levels of p‑NF‑κB, CINC and ENA‑78 were increased in lung tissue, and the expression levels of IL‑8, IL‑10 and the number of PMNs increased in serum and BALF. However, in comparison with the LPS group, the degree of lung injury was reduced in ARDS mice that were treated with PDTC. In addition, the expression level of p-NF-κB and the production of chemokines in lung tissue decreased in ARDS mice that were treated with PDTC, and the number of PMNs in BALF also decreased. In conclusion, the results of the present study suggest that the LPS‑induced phosphorylation of NF‑κB may result in the synthesis and release of CINC and ENA-78, which induce the accumulation of PMNs in the lung. Therefore, PDTC may be used to reduce the production of chemokines and cytokines, thereby decreasing the activation of PMNs in lung tissue and reducing the damage of lung tissue in ARDS.

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1	Ware LB and Matthay MA: The acute respiratory distress syndrome. N Engl J Med. 342:1334–1349. 2000. View Article : Google Scholar : PubMed/NCBI
2	Malhotra A: Low-tidal-volume ventilation in the acute respiratory distress syndrome. N Engl J Med. 357:1113–1120. 2007. View Article : Google Scholar : PubMed/NCBI
3	Meliton AY, Muñoz NM, Meliton LN, Binder DC, Osan CM, Zhu X, Dudek SM and Leff AR: Cytosolic group IVa phospholipase A2 mediates IL-8/CXCL8-induced transmigration of human polymorphonuclear leukocytes in vitro. J Inflamm (Lond). 7:142010. View Article : Google Scholar : PubMed/NCBI
4	Williams AE and Chambers RC: The mercurial nature of neutrophils: Still an enigma in ARDS? Am J Physiol Lung Cell Mol Physiol. 306:L217–L230. 2014. View Article : Google Scholar : PubMed/NCBI
5	Bhatia M and Moochhala S: Role of inflammatory mediators in the pathophysiology of acute respiratory distress syndrome. J Pathol. 202:145–156. 2004. View Article : Google Scholar : PubMed/NCBI
6	Giebelen IA, van Westerloo DJ, LaRosa GJ, de Vos AF and van der Poll T: Local stimulation of alpha7 cholinergic receptors inhibits LPS-induced TNF-alpha release in the mouse lung. Shock. 28:700–703. 2007.PubMed/NCBI
7	Nakayama S, Mukae H, Ishii H, Kakugawa T, Sugiyama K, Sakamoto N, Fujii T, Kadota J and Kohno S: Comparison of BALF concentrations of ENA-78 and IP10 in patients with idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia. Respir Med. 99:1145–1151. 2005. View Article : Google Scholar : PubMed/NCBI
8	Marcus BC, Wyble CW, Hynes KL and Gewertz BL: Cytokine-induced increases in endothelial permeability after adhesion molecule expression. Surg. 2006.120
9	Nooteboom A, van der Linden CJ and Hendriks T: Modulation of adhesion molecule expression on endothelial cells after induction by lipopolysaccharide-stimulated whole blood. Scand J Immunol. 59:440–448. 2004. View Article : Google Scholar : PubMed/NCBI
10	Guo YL, Huang H, Zeng DX, Zhao JP, Fang HJ and Lavoie JP: Interleukin (IL)-4 induces production of cytokine-induced neutrophil chemoattractants (CINCs) and intercellular adhesion molecule (ICAM)-1 in lungs of asthmatic rats. J Huazhong Univ Sci Technol. 33:470–478. 2013. View Article : Google Scholar
11	Ulich TR, Howard SC, Remick DG, Wittwer A, Yi ES, Yin S, Guo K, Welply JK and Williams JH: Intratracheal administration of endotoxin and cytokines. VI. Antiserum to CINC inhibits acute inflammation. Am J Physiol. 268(2 Pt 1): L245–L250. 1995.PubMed/NCBI
12	Lawrence T: The nuclear factor NF-kappaB pathway in inflammation. Cold Spring Harb Perspect Biol. 1:a0016512009. View Article : Google Scholar : PubMed/NCBI
13	May MJ and Ghosh S: Signal transduction through NF-kappa B. Immunol Today. 19:80–88. 1998. View Article : Google Scholar : PubMed/NCBI
14	Lawrence T, Gillroy DW, Colville-Nash PR and Willoughby DA: Possible new role for NF-kappaB in the resolution of inflammation. Nat Med. 7:1291–1297. 2001. View Article : Google Scholar : PubMed/NCBI
15	Kupfner JG, Arcaroli JJ, Yum HK, Nadler SG, Yang KY and Abraham E: Role of NF-kappaB in endotoxemia-induced alterations of lung neutrophil apoptosis. J Immunol. 167:7044–7051. 2001. View Article : Google Scholar : PubMed/NCBI
16	DeDiego ML, Nieto-Torres JL, Regla-Nava JA, Jimenez-Guardeño JM, Fernandez-Delgado R, Fett C, Castaño-Rodriguez C, Perlman S and Enjuanes L: Inhibition of NF-κB-mediated inflammation in severe acute respiratory syndrome coronavirus-infected mice increases survival. J Virol. 88:913–924. 2014. View Article : Google Scholar : PubMed/NCBI
17	Németh ZH, Haskó G and Vizi ES: Pyrrolidine dithiocarbamate augments IL-10, inhibits TNF-alpha, MIP-1alpha, IL-12, and nitric oxide production and protects from the lethal effect of endotoxin. Shock. 10:49–53. 1998. View Article : Google Scholar : PubMed/NCBI
18	Eren G, Cukurova Z, Hergunsel O, Demir G, Kucur M, Uslu E, Dalo E, Uhri M and Tugcu V: Protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate in lung injury in rats with streptozotocin-induced diabetes. Respiration. 79:402–410. 2010. View Article : Google Scholar : PubMed/NCBI
19	Keane MP, Belperio JA, Burdick MD, Lynch JP, Fishbein MC and Strieter RM: ENA-78 is an important angiogenic factor in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 164:2239–2242. 2001. View Article : Google Scholar : PubMed/NCBI
20	Wang H, Xu L, Zhao J, Wang D, Guo R, Wang J, Gong W, Liu T, Zhang Y and Dong L: Regulatory mechanism of pyrrolidine dithiocarbamate is mediated by nuclear factor-κB and inhibits neutrophil accumulation in ARDS mice. Exp Ther Med. 8:614–622. 2014.PubMed/NCBI
21	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCt method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
22	Christman JW, Lancaster LH and Blackwell TS: Nuclear factor kappa B: A pivotal role in the systemic inflammatory response syndrome and new target for therapy. Intensive Care Med. 24:1131–1138. 1998. View Article : Google Scholar : PubMed/NCBI
23	Chen X, Yang X, Liu T, Guan M, Feng X, Dong W, Chu X, Liu J, Tian X, Ci X, et al: Kaempferol regulates MAPKs and NF-κB signaling pathways to attenuate LPS-induced acute lung injury in mice. Int Immunopharmacol. 4:209–216. 2012. View Article : Google Scholar
24	Kang JL, Lee HW, Lee HS, Pack IS, Chong Y, Castranova V and Koh Y: Genistein prevents nuclear factor-kappa B activation and acute lung injury induced by lipopolysaccharide. Am J Resp Crit Care Med. 164:2206–2212. 2001. View Article : Google Scholar : PubMed/NCBI
25	Chignard M and Balloy V: Neutrophil recruitment and increased permeability during acute lung injury induced by lipopolysaccharide. Am J Physiol Lung Cell Mol Physiol. 279:L1083–L1090. 2000.PubMed/NCBI
26	Rahman A and Fazal F: Blocking NF-κB: An inflammatory issue. Proc Am Thorac Soc. 8:497–503. 2011. View Article : Google Scholar : PubMed/NCBI
27	Leverence JT, Medhora M, Konduri GG and Sampath V: Lipopolysaccharide-induced cytokine expression in alveolar epithelial cells: Role of PKCζ-mediated p47phox phosphorylation. Chem Biol Interact. 189:72–81. 2011. View Article : Google Scholar : PubMed/NCBI
28	Park WY, Goodman RB, Steinberg KP, Ruzinski JT, Radella F II, Park DR, Pugin J, Skerrett SJ, Hudson LD and Martin TR: Cytokine balance in the lungs of patients with acute respiratory distress syndrome. Am J Respir Crit Care Med. 164(10 Pt 1): 1894–1903. 2001.
29	Suratt BT and Parsons PE: Mechanisms of acute lung injury/acute respiratory distress syndrome. Clin Chest Med. 27:579–589, abstract viii. 2006. View Article : Google Scholar : PubMed/NCBI
30	Kunkel SL, Standiford T, Kasahara K and Strieter RM: Interleukin-8 (IL-8): The major neutrophil chemotactic factor in the lung. Exp Lung Res. 17:17–23. 1991. View Article : Google Scholar : PubMed/NCBI
31	Shen Y, Wang D and Wang X: Role of CCR2 and IL-8 in acute lung injury: A new mechanism and therapeutic target. Expert Rev Respir Med. 5:107–114. 2011. View Article : Google Scholar : PubMed/NCBI
32	Foulds KE, Rotte MJ and Seder RA: IL-10 is required for optimal CD8 T cell memory following Listeria monocytogenes infection. J Immunol. 177:2565–2574. 2006. View Article : Google Scholar : PubMed/NCBI
33	Lin CH, Cheng HW, Ma HP, Wu CH, Hong CY and Chen BC: Thrombin induces NF-kappaB activation and IL-8/CXCL8 expression in lung epithelial cells by a Rac1-dependent PI3K/Akt pathway. J Biol Chem. 286:10483–10494. 2011. View Article : Google Scholar : PubMed/NCBI
34	Lauzurica P, Martínez-Martínez S, Marazuela M, del Gómez Arco P, Martínez C, Sánchez-Madrid F and Redondo JM: Pyrrolidine dithiocarbamate protects mice from lethal shock induced by LPS or TNF-α. Eur J Immunol. 29:1890–1900. 1999. View Article : Google Scholar : PubMed/NCBI