The effect of down-regulation of CCL5 on lipopolysaccharide-induced WI-38 fibroblast injury: a potential role for infantile pneumonia | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 2، دوره 21، شماره 5، مرداد 2018، صفحه 449-454 اصل مقاله (887.31 K) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2018.27165.6640 | ||
| نویسندگان | ||
| Dong Bai؛ Anbang Han؛ Shan Cong* | ||
| Department of Pediatrics, Jining No. 1 People’s Hospital, Jining 272011, Shandong, China | ||
| چکیده | ||
| Objective(s): Aberrant expression of CCL5 has been found in several kinds of inflammatory diseases, and the roles of CCL5 in these diseases have also been reported. However, the role of CCL5 in infantile pneumonia is still unclear. Thus, the function and acting mechanism of CCL5 in the in vitro model of infantile pneumonia were researched in this study. Materials and Methods: Human fetal lung fibroblast WI-38 cells were subjected with lipopolysaccharide (LPS) to mimic an in vitro model of pneumonia. CCL5 was silenced by transfection with CCL5-targeted siRNA, and then cell viability, apoptosis, and the expressions of apoptosis-associated factors were respectively assessed by CCK-8 assay, flow cytometry and Western blot. Besides, expressions of CCL5 and pro-inflammatory factors were analyzed by qRT-PCR and Western blot. The secretions of pro-inflammatory factors were measured by ELISA. Finally, the expressions of main factors in JNK and NF-κB pathways were detected. Results: LPS treatment suppressed cell viability, promoted cell apoptosis, and enhanced the secretion of IL-6, MCP-1, and TNF-α. Overexpression of CCL5 was found in LPS-treated cells. CCL5 silence protected WI-38 cells from LPS-induced inflammatory damage, with increasing cell viability, inhibiting cell apoptosis, and reducing the production of pro-inflammatory cytokines. Besides, CCL5 silence inhibited LPS-induced activations of JNK and NF-κB pathways. Conclusion: Down-regulation of CCL5 could protect WI-38 cells from LPS-induced inflammatory damage via inactivating JNK and NF-κB pathways. | ||
| کلیدواژهها | ||
| CCL5؛ Infantile pneumonia؛ JNK pathway؛ Lipopolysaccharide (LPS)؛ NF-κB pathway؛ Pro-inflammatory cytokines | ||
| مراجع | ||
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1. Wardlaw T, Salama P, Johansson EW, Mason E. Pneumonia: the leading killer of children. Lancet 2006; 368:1048˗1050. 2. Chen CH, Wen HJ, Chen PC, Lin SJ, Chiang TL, Hsieh IC, et al. Prenatal and postnatal risk factors for infantile pneumonia in a representative birth cohort. Epidemiol Infect 2012; 140:1277˗1285. 3. Yao YQ, Wang ZW, Ding YX, Yu Y, Jiang WX, Liu XH, et al. Effect of Zhifei mixture combined western drugs on symptoms and signs of children with mycoplasma pneumonia. Zhongguo Zhong Xi Yi Jie He Za Zhi 2014; 34:522˗525. 4. Hu HF, Cao LJ. Treatment of pediatric pneumonia. J Applie Clin Pediatr 2011; 4:3. 5. Coussens LM, Werb Z. Inflammation and cancer. Nature 2002; 420:860˗867. 6. Schall TJ, Jongstra J, Dyer BJ, Jorgensen J, Clayberger C, Davis MM, et al. A human T cell-specific molecule is a member of a new gene family. J Immunol 1988; 141:1018˗1025. 7. Huang CY, Fong YC, Lee CY, Chen MY, Tsai HC, Hsu HC, et al. CCL5 increases lung cancer migration via PI3K, Akt and NF-kappaB pathways. Biochem Pharmacol 2009; 77:794˗803. 8. Singh S, Sadanandam A, Singh RK. Chemokines in tumor angiogenesis and metastasis. Cancer Metastasis Rev 2007; 26:453˗467. 9. Mccormack G, Moriarty D, O’Donoghue DP, Mccormick PA, Sheahan K, Baird AW. Tissue cytokine and chemokine expression in inflammatory bowel disease. Inflamm Res 2001; 50:491-495. 10. Ben-Baruch A. Inflammation-associated immune suppression in cancer: the roles played by cytokines, chemokines and additional mediators. Semin Cancer Biol 2006; 16:38-52. 11. Pinilla S, Alt E, Abdul Khalek FJ, Jotzu C, Muehlberg F, Beckmann C, et al. Tissue resident stem cells produce CCL5 under the influence of cancer cells and thereby promote breast cancer cell invasion. Cancer Lett 2009; 284:80˗85. 12. Chuang JY, Yang WH, Chen HT, Huang CY, Tan TW, Lin YT, et al. CCL5/CCR5 axis promotes the motility of human oral cancer cells. J Cell Physiol 2009; 220:418-426. 13. Smeding L, Kuiper JW, Plotz FB, Kneyber MC, Groeneveld AJ. Aggravation of myocardial dysfunction by injurious mechanical ventilation in LPS-induced pneumonia in rats. Respir Res 2013; 14:92. 14. Silswal N, Singh AK, Aruna B, Mukhopadhyay S, Ghosh S, Ehtesham NZ. Human resistin stimulates the pro-inflammatory cytokines TNF-α and IL-12 in macrophages by NF-κB-dependent pathway. Biochem Biophys Res Commun 2005; 334:1092˗1101. 15. Zeidler D, Zahringer U, Gerber I, Dubery I, Hartung T, Bors W, et al. Innate immunity in Arabidopsis thaliana: lipopolysaccharides activate nitric oxide synthase (NOS) and induce defense genes. Proc Natl Acad Sci U S A 2004; 101:15811˗15816. 16. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001; 25:402˗408. 17. Wang Y, Dong H, Zhu M, Ou Y, Zhang J, Luo H, et al. Icariin exterts negative effects on human gastric cancer cell invasion and migration by vasodilator-stimulated phosphoprotein via Rac1 pathway. Eur J Pharmacol 2010; 635:40˗48. 18. Jiang YZ. Pseudomonas aeruginosa colonization increased the ventilator-associated pneumonia in mice through the TNF-α and JNK signaling pathway. Biol Sci 2014; 14:66. 19. Hwang MH, Damte D, Lee JS, Gebru E, Chang ZQ, Cheng H, et al. Mycoplasma hyopneumoniae induces pro-inflammatory cytokine and nitric oxide production through NFκB and MAPK pathways in RAW264.7 cells. Vet Res Commun 2011; 35:21-34. 20. Shou-Jun LI, Zhang Y, Neng-Shun WU, Sun JH. Detection of serum IL-6, IL-10 and TNF-α in children with mycoplasma pneumonia and their relationship with disease severity. J Nanchang Univ 2012; 4:432. 21. Wang AG. Significance of serum levels of MCP˗1 and interleukin˗12P40 in children infected with mycoplasma pneumonia. Modern Prev Med 2009; 36:3582˗3585. 22. Fessele S, Boehlk S, Mojaat A, Miyamoto NG, Werner T, Nelson EL, et al. Molecular and in silico characterization of a promoter module and C/EBP element that mediate LPS-induced RANTES/CCL5 expression in monocytic cells. FASEB J 2001; 15:577˗579. 23. Castellani ML, Shanmugham LN, Petrarca C, Simeonidou I, Frydas S, Colli MD, et al. Expression and secretion of RANTES (CCL5) in granulomatous calcified tissue before and after lipopolysaccharide treatment In Vivo. Calcif Tissue Int 2007; 80:60˗67. 24. Appay V, Rowland-Jones SL. RANTES: a versatile and controversial chemokine. Trends Immunol 2001; 22:83˗87. 25. Gerdes N, Zhu L, Ersoy M, Hermansson A, Hjemdahl P, Hu H, et al. Platelets regulate CD4⁺ T-cell differentiation via multiple chemokines in humans. Thromb Haemost 2011; 106:353˗362. 26. Sakthivel SK, Singh UP, Singh S, Taub DD, Igietseme JU, Lillard Jr JW. CCL5 regulation of mucosal chlamydial immunity and infection. BMC Microbiol 2008; 8:136. 27. Mckinley L, Logar AJ, Mcallister F, Zheng M, Steele C, Kolls JK. Regulatory T cells dampen pulmonary inflammation and lung injury in an animal model of pneumocystis pneumonia. J Immunol 2006; 177:6215˗6226. 28. Marques RE, Guabiraba R, Russo RC, Teixeira MM. Targeting CCL5 in inflammation. Expert Opin Ther Targets 2013; 17:1439˗1460. 29. Barnes DA, Tse J, Kaufhold M, Owen M, Hesselgesser J, Strieter R, et al. Polyclonal antibody directed against human RANTES ameliorates disease in the Lewis rat adjuvant-induced arthritis model. J Clin Invest 1998; 101:2910˗2919. 30. Ling M, Li Y, Xu Y, Pang Y, Shen L, Jiang R, et al. Regulation of miRNA˗21 by reactive oxygen species-activated ERK/NF-κB in arsenite-induced cell transformation. Free Radic Biol Med 2012; 52:1508˗1518. 31. Han DW, Lee MH, Kim HH, Hyon SH, Park JC. Epigallocatechin-3-gallate regulates cell growth, cell cycle and phosphorylated nuclear factor-[kappa]B in human dermal fibroblasts. Acta Pharmacol Sin 2011; 32:637˗646. 32. Johnson GL, Lapadat R. Mitogen-activated protein kinase pathways mediated by ERK, JNK, and p38 protein kinases. Science 2002; 298:1911˗1912. 33. Liu D, Cao G, Han L, Ye Y, Sima Y, Ge W. Flavonoids from radix tetrastigmae inhibit TLR4/MD-2 mediated JNK and NF-κB pathway with anti-inflammatory properties. Cytokine 2016; 84:29-36. | ||
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