title: Role of ribonuclease L in viral pathogen-associated molecular pattern/influenza virus and cigarette smoke-induced inflammation and remodeling.
abstract: Interactions between cigarette smoke (CS) exposure and viral infection play an important role(s) in the pathogenesis of chronic obstructive pulmonary disease and a variety of other disorders. A variety of lines of evidence suggest that this interaction induces exaggerated inflammatory, cytokine, and tissue remodeling responses. We hypothesized that the 2'-5' oligoadenylate synthetase (OAS)/RNase L system, an innate immune antiviral pathway, plays an important role in the pathogenesis of these exaggerated responses. To test this hypothesis, we characterize the activation of 2'-5' OAS in lungs from mice exposed to CS and viral pathogen-associated molecular patterns (PAMPs)/live virus, alone and in combination. We also evaluated the inflammatory and remodeling responses induced by CS and virus/viral PAMPs in lungs from RNase L null and wild-type mice. These studies demonstrate that CS and viral PAMPs/live virus interact in a synergistic manner to stimulate the production of select OAS moieties. They also demonstrate that RNase L plays a critical role in the pathogenesis of the exaggerated inflammatory, fibrotic, emphysematous, apoptotic, TGF-β1, and type I IFN responses induced by CS plus virus/viral PAMP in combination. These studies demonstrate that CS is an important regulator of antiviral innate immunity, highlight novel roles of RNase L in CS plus virus induced inflammation, tissue remodeling, apoptosis, and cytokine elaboration and highlight pathways that may be operative in chronic obstructive pulmonary disease and mechanistically related disorders.
authors.affiliation: Section of Pulmonary and Critical Care Medicine, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhou
authors.forename: Min-Jong
authors.initials: MJ
authors.lastname: Kang
authors.forename: Babal Kant
authors.initials: BK
authors.lastname: Jha
authors.forename: Robert H
authors.initials: RH
authors.lastname: Silverman
authors.forename: Chun Geun
authors.initials: CG
authors.lastname: Lee
authors.forename: Jack A
authors.initials: JA
authors.lastname: Elias
mesh_terms: D056151:Airway Remodeling / Q000502:physiology*; D000818:Animals; D004722:Endoribonucleases / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005455:Fluorescent Antibody Technique; D020287:In Situ Nick-End Labeling; D007249:Inflammation / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D009980:Influenza A virus; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000150:complications* / Q000201:enzymology; D029424:Pulmonary Disease, Chronic Obstructive / Q000201:enzymology / Q000473:pathology; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*
chemical_list: D014028:Tobacco Smoke Pollution; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease
references.citation: J Interferon Cytokine Res. 2011 Jan;31(1):49-57
references.pmid: 21190483
references.citation: J Biol Chem. 1988 Apr 5;263(10):4945-9
references.pmid: 3350819
references.citation: Am J Public Health. 1993 Sep;83(9):1277-83
references.pmid: 8363004
references.citation: J Immunol. 2009 Dec 15;183(12):8035-43
references.pmid: 19923450
references.citation: Eur Respir J. 2004 Feb;23(2):327-33
references.pmid: 14979512
references.citation: Thorax. 2000 Feb;55(2):114-20
references.pmid: 10639527
references.citation: N Engl J Med. 2004 Jun 24;350(26):2635-7
references.pmid: 15215476
references.citation: Am J Respir Crit Care Med. 2006 Dec 15;174(12):1342-51
references.pmid: 17023734
references.citation: Chest. 2000 May;117(5 Suppl 1):303S-17S
references.pmid: 10843965
references.citation: J Biol Chem. 1995 Jun 2;270(22):13308-17
references.pmid: 7539425
references.citation: Thorax. 2006 Mar;61(3):250-8
references.pmid: 16517585
references.citation: J Virol. 1982 Jun;42(3):1039-45
references.pmid: 6178844
references.citation: Diabetes. 2005 May;54(5):1588-91
references.pmid: 15855350
references.citation: J Infect Dis. 2005 Nov 15;192(10):1741-8
references.pmid: 16235172
references.citation: J Interferon Cytokine Res. 2002 Sep;22(9):981-93
references.pmid: 12396720
references.citation: Nature. 1987 Dec 10-16;330(6148):587-8
references.pmid: 2825034
references.citation: J Interferon Res. 1989 Dec;9(6):649-57
references.pmid: 2481699
references.citation: J Interferon Cytokine Res. 2011 Jan;31(1):41-7
references.pmid: 21142819
references.citation: Nature. 1979 Dec 6;282(5739):582-6
references.pmid: 95208
references.citation: N Engl J Med. 2004 Jun 24;350(26):2689-97
references.pmid: 15215485
references.citation: J Immunol. 2010 Apr 15;184(8):4460-9
references.pmid: 20228194
references.citation: Am J Respir Crit Care Med. 2001 Nov 1;164(9):1618-23
references.pmid: 11719299
references.citation: N Engl J Med. 1982 Oct 21;307(17):1042-6
references.pmid: 7121513
references.citation: Nucleic Acids Res. 1981 Apr 10;9(7):1571-81
references.pmid: 6164990
references.citation: J Interferon Cytokine Res. 1998 Nov;18(11):953-61
references.pmid: 9858317
references.citation: J Virol. 1983 Jun;46(3):1051-5
references.pmid: 6190010
references.citation: J Biol Chem. 1987 Mar 15;262(8):3852-7
references.pmid: 2434505
references.citation: Am J Med. 2003 Sep;115(4):272-7
references.pmid: 12967691
references.citation: Proc Am Thorac Soc. 2004;1(2):115-20
references.pmid: 16113423
references.citation: Int J Tuberc Lung Dis. 2008 Apr;12(4):361-7
references.pmid: 18371259
references.citation: J Biol Chem. 1996 May 31;271(22):13184-90
references.pmid: 8662694
references.citation: Am J Respir Crit Care Med. 2006 May 15;173(10):1114-21
references.pmid: 16484677
references.citation: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7100-5
references.pmid: 16627618
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Nov;289(5):L711-21
references.pmid: 15734789
references.citation: N Engl J Med. 2004 Jun 24;350(26):2645-53
references.pmid: 15215480
references.citation: Arch Intern Med. 2004 Nov 8;164(20):2206-16
references.pmid: 15534156
references.citation: Eur J Biochem. 1999 Sep;264(3):687-701
references.pmid: 10491114
references.citation: Respir Res. 2006 Mar 30;7:53
references.pmid: 16571143
references.citation: Chest. 2006 Oct;130(4):1203-10
references.pmid: 17035457
references.citation: J Virol. 2006 Mar;80(6):2987-99
references.pmid: 16501108
references.citation: J Virol. 1984 Apr;50(1):220-8
references.pmid: 6422053
references.citation: J Exp Med. 1997 Sep 15;186(6):967-72
references.pmid: 9294150
references.citation: J Allergy Clin Immunol. 2004 Oct;114(4):715-24; quiz 725
references.pmid: 15480305
references.citation: J Virol. 2007 Dec;81(23):12720-9
references.pmid: 17804500
references.citation: Am J Public Health. 1981 May;71(5):530-2
references.pmid: 7212144
references.citation: J Immunol. 2012 May 1;188(9):4468-75
references.pmid: 22467655
references.citation: J Immunol. 2005 Jul 15;175(2):1100-6
references.pmid: 16002711
references.citation: Curr Opin Pharmacol. 2007 Jun;7(3):252-8
references.pmid: 17369093
references.citation: J Clin Invest. 2008 Aug;118(8):2771-84
references.pmid: 18654661
references.citation: Respir Res. 2009 Nov 12;10:107
references.pmid: 19909524
references.citation: EMBO J. 1997 Nov 3;16(21):6355-63
references.pmid: 9351818
references.citation: J Interferon Cytokine Res. 2000 Dec;20(12):1091-100
references.pmid: 11152576
references.citation: J Biol Chem. 2001 Dec 21;276(51):48473-82
references.pmid: 11585831
references.citation: Chest. 1995 Aug;108(2 Suppl):43S-52S
references.pmid: 7634925
references.citation: Biochimie. 2007 Jun-Jul;89(6-7):789-98
references.pmid: 17400356
references.citation: Nature. 2007 Aug 16;448(7155):816-9
references.pmid: 17653195