Analysis of mechanical ventilation and lipopolysaccharide‑induced acute lung injury using DNA microarray analysis

Chen,Yuqing; Zhou,Xin; Rong,Ling

doi:10.3892/mmr.2015.3335

Analysis of mechanical ventilation and lipopolysaccharide‑induced acute lung injury using DNA microarray analysis

Authors:
- Yuqing Chen
- Xin Zhou
- Ling Rong
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Affiliations: Department of Respiratory Medicine, Shanghai First People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200080, P.R. China, Department of Respiratory Medicine, The People's Hospital of Bozhou, Bozhou, Anhui 236804, P.R. China
Published online on: February 11, 2015 https://doi.org/10.3892/mmr.2015.3335
Pages: 4239-4245
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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Abstract

Gene expression profiles of samples taken from patients with acute lung injury (ALI) induced by mechanical ventilation (MV) and lipopolysaccharide (LPS) were analyzed in order to identify key genes, and explore the underlying mechanisms. The GSE2411 microarray data set was downloaded from the Gene Expression Omnibus. This data set contained microarray data from 24 mouse lung samples, which were equally divided into four groups: Control group, MV group, LPS group and MV+LPS group. Differentially expressed genes (DEGs) were identified in the MV, LPS and MV+LPS groups, as compared with the control group, using packages of R software. Hierarchical clustering and between‑group comparisons were performed for each group of DEGs. Overrepresented biological processes were revealed by functional enrichment analysis using the Database for Annotation, Visualization and Integrated Discovery. Unique DEGs in the LPS and MV+LPS groups were selected, and pathway enrichment analyses were performed using the Kyoto Encyclopedia of Genes and Genomes Orthology Based Annotation system. A total of 32, 264 and 685 DEGs were identified in the MV, LPS and MV+LPS groups, respectively. The MV+LPS group had more DEGs, as compared with the other two treatment groups. Genes associated with the immune and inflammatory responses were significantly overrepresented in both the LPS and MV+LPS groups, suggesting that LPS dominated the progression of ALI. Unique DEGs in the LPS and MV+LPS groups were associated with cytokine‑cytokine receptor interaction. The Janus kinase‑signal transducer and activator of transcription signaling pathway was shown to be enriched in the LPS+MV‑unique DEGs. The results of the present study demonstrated that MV could exaggerate the transcriptional response of the lungs to LPS. Numerous key genes were identified, which may advance knowledge regarding the pathogenesis of ALI.

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1	Bernard GR, Artigas A, Brigham KL, et al: The American-European Consensus Conference on ARDS. Definitions, mechanisms, relevant outcomes, and clinical trial coordination. Am J Respir Crit Care Med. 149:818–824. 1994. View Article : Google Scholar : PubMed/NCBI
2	Goodman RB, Pugin J, Lee JS and Matthay MA: Cytokine-mediated inflammation in acute lung injury. Cytokine Growth Factor Rev. 14:523–535. 2003. View Article : Google Scholar : PubMed/NCBI
3	Dolinay T, Kim YS, Howrylak J, et al: Inflammasome-regulated cytokines are critical mediators of acute lung injury. Am J Respir Crit Care Med. 185:1225–1234. 2012. View Article : Google Scholar : PubMed/NCBI
4	Bhatia M, Zemans RL and Jeyaseelan S: Role of chemokines in the pathogenesis of acute lung injury. Am J Respir Cell Mol Biol. 46:566–572. 2012. View Article : Google Scholar : PubMed/NCBI
5	Abraham E, Arcaroli J, Carmody A, Wang H and Tracey KJ: HMG-1 as a mediator of acute lung inflammation. J Immunol. 165:2950–2954. 2000. View Article : Google Scholar : PubMed/NCBI
6	Imai Y, Kuba K, Neely GG, et al: Identification of oxidative stress and Toll-like receptor 4 signaling as a key pathway of acute lung injury. Cell. 133:235–249. 2008. View Article : Google Scholar : PubMed/NCBI
7	Mei SH, McCarter SD, Deng Y, et al: Prevention of LPS-induced acute lung injury in mice by mesenchymal stem cells overexpressing angiopoietin 1. PLoS Med. 4:e2692007. View Article : Google Scholar : PubMed/NCBI
8	Kawasaki M, Kuwano K, Hagimoto N, et al: Protection from lethal apoptosis in lipopolysaccharide-induced acute lung injury in mice by a caspase inhibitor. Am J Pathol. 157:597–603. 2000. View Article : Google Scholar : PubMed/NCBI
9	Inoue K, Takano H, Yanagisawa R, et al: Protective role of urinary trypsin inhibitor in acute lung injury induced by lipopolysaccharide. Exp Biol Med (Maywood). 230:281–287. 2005.
10	Peng X, Hassoun PM, Sammani S, et al: Protective effects of sphingosine 1-phosphate in murine endotoxin-induced inflammatory lung injury. Am J Respir Crit Care Med. 169:1245–1251. 2004. View Article : Google Scholar : PubMed/NCBI
11	Li T, Zhang J, Feng J, et al: Resveratrol reduces acute lung injury in a LPS-induced sepsis mouse model via activation of Sirt1. Mol Med Rep. 7:1889–1895. 2013.PubMed/NCBI
12	Rittirsch D, Flierl MA, Day DE, et al: Acute lung injury induced by lipopolysaccharide is independent of complement activation. J Immunol. 180:7664–7672. 2008. View Article : Google Scholar : PubMed/NCBI
13	López-Cuenca S, Morales-García S, Martín-Hita A, Frutos-Vivar F, Fernández-Segoviano P and Esteban A: Severe acute respiratory failure secondary to acute fibrinous and organizing pneumonia requiring mechanical ventilation: a case report and literature review. Respir Care. 57:1337–1341. 2012. View Article : Google Scholar : PubMed/NCBI
14	Bouferrache K and Vieillard-Baron A: Acute respiratory distress syndrome, mechanical ventilation, and right ventricular function. Curr Opin Crit Care. 17:30–35. 2011. View Article : Google Scholar
15	Slutsky AS: Lung injury caused by mechanical ventilation. Chest J. 116:9S–15S. 1999. View Article : Google Scholar
16	Gajic O, Dara SI, Mendez JL, et al: Ventilator-associated lung injury in patients without acute lung injury at the onset of mechanical ventilation. Crit Care Med. 32:1817–1824. 2004. View Article : Google Scholar : PubMed/NCBI
17	Ranieri VM, Suter PM, Tortorella C, et al: Effect of mechanical ventilation on inflammatory mediators in patients with acute respiratory distress syndrome: a randomized controlled trial. JAMA. 282:54–61. 1999. View Article : Google Scholar : PubMed/NCBI
18	Altemeier WA, Matute-Bello G, Gharib SA, Glenny RW, Martin TR and Liles WC: Modulation of lipopolysaccharide-induced gene transcription and promotion of lung injury by mechanical ventilation. J Immunol. 175:3369–3376. 2005. View Article : Google Scholar : PubMed/NCBI
19	Barrett T, Suzek TO, Troup DB, et al: NCBI GEO: mining millions of expression profiles - database and tools. Nucleic Acids Res. 33:D562–D566. 2005. View Article : Google Scholar
20	Fujita A, Sato JR, Rodrigues Lde O, Ferreira CE and Sogayar MC: Evaluating different methods of microarray data normalization. BMC Bioinformatics. 7:4692006. View Article : Google Scholar : PubMed/NCBI
21	Smyth GK: Limma: linear models for microarray data. Bioinformatics and computational biology solutions using R and Bioconductor. Gentleman R, Carey VM Dudoit S, Irizarry R and Huber W: Springer; New York: pp. 397–420. 2005, View Article : Google Scholar
22	Benjamini Y and Hochberg Y: Controlling the false discovery rate: a practical and powerful approach to multiple testing. J Roy Statist Soc Ser B (Methodological). 57:289–300. 1995.
23	Eisen MB, Spellman PT, Brown PO and Botstein D: Cluster analysis and display of genome-wide expression patterns. Proc Natl Acad Sci USA. 95:14863–14868. 1998. View Article : Google Scholar : PubMed/NCBI
24	Hsu CL and Lee WC: Detecting differentially expressed genes in heterogeneous diseases using half Student’s t-test. Int J Epidemiol. 39:1597–1604. 2010. View Article : Google Scholar : PubMed/NCBI
25	Huang da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
26	Wu J, Mao X, Cai T, Luo J and Wei L: KOBAS server: a web-based platform for automated annotation and pathway identification. Nucleic Acids Res. 34:W720–W724. 2006. View Article : Google Scholar : PubMed/NCBI
27	Xie C, Mao X, Huang J, et al: KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Res. 39:W316–W322. 2011. View Article : Google Scholar : PubMed/NCBI
28	Luster AD: Chemokines - chemotactic cytokines that mediate inflammation. N Engl J Med. 338:436–445. 1998. View Article : Google Scholar : PubMed/NCBI
29	Murphy TJ, Paterson HM, Kriynovich S, et al: Linking the "two-hit" response following injury to enhanced TLR4 reactivity. J Leukoc Biol. 77:16–23. 2005.
30	Jin L, Batra S, Douda DN, Palaniyar N and Jeyaseelan S: CXCL1 Contributes to Host Defense in Polymicrobial Sepsis via Modulating T Cell and Neutrophil Functions. J Immunol. 193:3549–3558. 2014. View Article : Google Scholar : PubMed/NCBI
31	De Filippo K, Dudeck A, Hasenberg M, et al: Mast cell and macrophage chemokines CXCL1/CXCL2 control the early stage of neutrophil recruitment during tissue inflammation. Blood. 121:4930–4937. 2013. View Article : Google Scholar : PubMed/NCBI
32	Mihara M, Hashizume M, Yoshida H, Suzuki M and Shiina M: IL-6/IL-6 receptor system and its role in physiological and pathological conditions. Clin Sci (Lond). 122:143–159. 2012. View Article : Google Scholar
33	Rose-John S: IL-6 trans-signaling via the soluble IL-6 receptor: importance for the pro-inflammatory activities of IL-6. Int J Biol Sci. 8:1237–1247. 2012. View Article : Google Scholar : PubMed/NCBI
34	Ahuja N, Andres-Hernando A, Altmann C, et al: Circulating IL-6 mediates lung injury via CXCL1 production after acute kidney injury in mice. Am J Physiol Renal Physiol. 303:F864–F872. 2012. View Article : Google Scholar : PubMed/NCBI
35	Dinarello CA: Blocking interleukin-1β in acute and chronic autoinflammatory diseases. J Intern Med. 269:16–28. 2011. View Article : Google Scholar :
36	Kolb M, Margetts PJ, Anthony DC, Pitossi F and Gauldie J: Transient expression of IL-1beta induces acute lung injury and chronic repair leading to pulmonary fibrosis. J Clin Invest. 107:1529–1536. 2001. View Article : Google Scholar : PubMed/NCBI
37	Rose CE Jr, Sung SS and Fu SM: Significant involvement of CCL2 (MCP-1) in inflammatory disorders of the lung. Microcirculation. 10:273–288. 2003. View Article : Google Scholar : PubMed/NCBI
38	Parsons PE, Matthay MA, Ware LB and Eisner MD; National Heart, Lung, Blood Institute Acute Respiratory Distress Syndrome Clinical Trials Network: Elevated plasma levels of soluble TNF receptors are associated with morbidity and mortality in patients with acute lung injury. Am J Physiol Lung Cell Mol Physiol. 288:L426–L431. 2005. View Article : Google Scholar
39	Jeon GW, Sung DK, Jung YJ, et al: Granulocyte colony stimulating factor attenuates hyperoxia-induced lung injury by down-modulating inflammatory responses in neonatal rats. Yonsei Med J. 52:65–73. 2011. View Article : Google Scholar :
40	Standiford LR, Standiford TJ, Newstead MJ, et al: TLR4-dependent GM-CSF protects against lung injury in Gram-negative bacterial pneumonia. Am J Physiol Lung Cell Mol Physiol. 302:L447–L454. 2012. View Article : Google Scholar :
41	Yamaguchi T, Miyata Y, Hayamizu K, et al: Preventive effect of G-CSF on acute lung injury via alveolar macrophage regulation. J Surg Res. 178:378–384. 2012. View Article : Google Scholar : PubMed/NCBI
42	Darnell JE Jr, Kerr IM and Stark GR: Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science. 264:1415–1421. 1994. View Article : Google Scholar : PubMed/NCBI
43	O’Shea JJ, Gadina M and Schreiber RD: Cytokine signaling in 2002: new surprises in the Jak/Stat pathway. Cell. 109:S121–S131. 2002. View Article : Google Scholar
44	Severgnini M, Takahashi S, Rozo LM, et al: Activation of the STAT pathway in acute lung injury. Am J Physiol Lung Cell Mol Physiol. 286:L1282–L1292. 2004. View Article : Google Scholar : PubMed/NCBI
45	Gao H, Guo RF, Speyer CL, et al: Stat3 activation in acute lung injury. J Immunol. 172:7703–7712. 2004. View Article : Google Scholar : PubMed/NCBI
46	Severgnini M, Takahashi S, Tu P, et al: Inhibition of the Src and Jak kinases protects against lipopolysaccharide-induced acute lung injury. Am J Respir Crit Care Med. 171:858–867. 2005. View Article : Google Scholar : PubMed/NCBI
47	Tchatalbachev S, Ghai R, Hossain H and Chakraborty T: Gram-positive pathogenic bacteria induce a common early response in human monocytes. BMC Microbiol. 10:2752010. View Article : Google Scholar : PubMed/NCBI
48	Hierholzer C, Kelly E, Lyons V, et al: G-CSF instillation into rat lungs mediates neutrophil recruitment, pulmonary edema and hypoxia. J Leukoc Biol. 63:169–174. 1998.PubMed/NCBI
49	Suratt BT, Eisner MD, Calfee CS, et al: NHLBI Acute Respiratory Distress Syndrome Network: Plasma granulocyte colony-stimulating factor levels correlate with clinical outcomes in patients with acute lung injury. Crit Care Med. 37:1322–1328. 2009. View Article : Google Scholar : PubMed/NCBI
50	Shin YS, Takeda K, Shiraishi Y, et al: Inhibition of Pim1 kinase activation attenuates allergen-induced airway hyperresponsiveness and inflammation. Am J Respir Cell Mol Biol. 46:488–497. 2012. View Article : Google Scholar :
51	Murray MJ, Kumar M, Gregory TJ, et al: Select dietary fatty acids attenuate cardiopulmonary dysfunction during acute lung injury in pigs. Am J Physiol. 269:H2090–H2099. 1995.PubMed/NCBI
52	Rice TW, Wheeler AP, Thompson BT, et al: NIH NHLBI Acute Respiratory Syndrome Network of Investigators: Enteral omega-3 fatty acid, gamma-linolenic acid, and antioxidant supplementation in acute lung injury. JAMA. 306:1574–1581. 2011. View Article : Google Scholar : PubMed/NCBI