title: Protective role of interleukin-10 in ozone-induced pulmonary inflammation.
abstract: BACKGROUND
  The mechanisms underlying ozone (O₃)-induced pulmonary inflammation remain unclear. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is known to inhibit inflammatory mediators.
  
  
  OBJECTIVE
  We investigated the molecular mechanisms underlying interleuken-10 (IL-10)-mediated attenuation of O₃-induced pulmonary inflammation in mice.
  
  
  METHODS
  Il10-deficient (Il10(-/-)) and wild-type (Il10(+/+)) mice were exposed to 0.3 ppm O₃ or filtered air for 24, 48, or 72 hr. Immediately after exposure, differential cell counts and total protein (a marker of lung permeability) were assessed from bronchoalveolar lavage fluid (BALF). mRNA and protein levels of cellular mediators were determined from lung homogenates. We also used global mRNA expression analyses of lung tissue with Ingenuity Pathway Analysis to identify patterns of gene expression through which IL-10 modifies O₃-induced inflammation.
  
  
  RESULTS
  Mean numbers of BALF polymorphonuclear leukocytes (PMNs) were significantly greater in Il10(-/-) mice than in Il10(+/+) mice after exposure to O₃ at all time points tested. O₃-enhanced nuclear NF-κB translocation was elevated in the lungs of Il10(-/-) compared with Il10(+/+) mice. Gene expression analyses revealed several IL-10-dependent and O₃-dependent mediators, including macrophage inflammatory protein 2, cathepsin E, and serum amyloid A3.
  
  
  CONCLUSIONS
  Results indicate that IL-10 protects against O₃-induced pulmonary neutrophilic inflammation and cell proliferation. Moreover, gene expression analyses identified three response pathways and several genetic targets through which IL-10 may modulate the innate and adaptive immune response. These novel mechanisms of protection against the pathogenesis of O₃-induced pulmonary inflammation may also provide potential therapeutic targets to protect susceptible individuals.
authors.affiliation: National Institute of Environmental Health Sciences, Laboratory of Respiratory Biology, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina 27709, USA.
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Backus
authors.forename: Reuben
authors.initials: R
authors.lastname: Howden
authors.forename: Jennifer
authors.initials: J
authors.lastname: Fostel
authors.forename: Alison K
authors.initials: AK
authors.lastname: Bauer
authors.forename: Hye-Youn
authors.initials: HY
authors.lastname: Cho
authors.forename: Jacqui
authors.initials: J
authors.lastname: Marzec
authors.forename: David B
authors.initials: DB
authors.lastname: Peden
authors.forename: Steven R
authors.initials: SR
authors.lastname: Kleeberger
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D051940:B7-2 Antigen / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054426:Chemokine CXCL2 / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010126:Ozone / Q000633:toxicity*; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000393:Air Pollutants; D051940:B7-2 Antigen; D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D012333:RNA, Messenger; D016753:Interleukin-10; D010126:Ozone
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L390-7
references.pmid: 15516495
references.citation: Arthritis Rheum. 2009 Mar;60(3):738-49
references.pmid: 19248109
references.citation: Lancet. 2002 Feb 2;359(9304):386-91
references.pmid: 11844508
references.citation: Biochem Biophys Res Commun. 1992 Feb 14;182(3):1155-9
references.pmid: 1371674
references.citation: Immunol Rev. 2008 Dec;226:172-90
references.pmid: 19161424
references.citation: Toxicol Sci. 2001 Sep;63(1):115-24
references.pmid: 11509751
references.citation: J Interferon Cytokine Res. 1999 Jun;19(6):563-73
references.pmid: 10433356
references.citation: Clin Exp Allergy. 2002 Mar;32(3):391-6
references.pmid: 11940069
references.citation: Eur Respir J. 2010 Aug;36(2):428-37
references.pmid: 20032013
references.citation: J Immunol. 1993 Aug 1;151(3):1224-34
references.pmid: 7687627
references.citation: Mol Cell Biochem. 2002 May-Jun;234-235(1-2):91-8
references.pmid: 12162464
references.citation: J Immunol. 1994 Dec 1;153(11):5190-9
references.pmid: 7525726
references.citation: Int Arch Allergy Immunol. 2009;148(2):99-108
references.pmid: 18799889
references.citation: J Immunol. 1995 Aug 15;155(4):2222-9
references.pmid: 7636269
references.citation: Am J Respir Crit Care Med. 2007 Apr 15;175(8):829-39
references.pmid: 17255564
references.citation: Am J Respir Cell Mol Biol. 2002 Apr;26(4):413-9
references.pmid: 11919077
references.citation: Mol Aspects Med. 2000 Feb-Apr;21(1-2):1-48
references.pmid: 10804262
references.citation: Mol Pharmacol. 2007 Feb;71(2):609-18
references.pmid: 17108260
references.citation: Cytokine. 2005 Mar 7;29(5):215-28
references.pmid: 15760678
references.citation: Toxicol Lett. 1999 Oct 29;110(1-2):35-42
references.pmid: 10593593
references.citation: J Allergy Clin Immunol. 2005 Feb;115(2):405-11
references.pmid: 15696103
references.citation: Clin Exp Allergy. 2005 Jul;35(7):914-9
references.pmid: 16008678
references.citation: Nat Rev Drug Discov. 2002 Jan;1(1):55-64
references.pmid: 12119610
references.citation: Environ Health Perspect. 1995 Mar;103 Suppl 2:77-89
references.pmid: 7614952
references.citation: N Engl J Med. 2009 Mar 12;360(11):1085-95
references.pmid: 19279340
references.citation: Am J Respir Cell Mol Biol. 1998 Jan;18(1):51-9
references.pmid: 9448045
references.citation: Br J Pharmacol. 2002 Jul;136(5):735-45
references.pmid: 12086983
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Feb;280(2):L326-33
references.pmid: 11159012
references.citation: Am J Respir Crit Care Med. 2000 Jan;161(1):249-56
references.pmid: 10619828
references.citation: Toxicol Appl Pharmacol. 1993 Apr;119(2):306-9
references.pmid: 8480341
references.citation: J Immunol. 2003 Sep 15;171(6):3119-27
references.pmid: 12960338
references.citation: Biochem Biophys Res Commun. 2008 Mar 14;367(3):517-22
references.pmid: 18178150
references.citation: J Immunol. 2002 Jun 15;168(12):6404-11
references.pmid: 12055259
references.citation: Expert Opin Ther Targets. 2007 Jul;11(7):869-80
references.pmid: 17614756
references.citation: Am J Respir Cell Mol Biol. 1998 Sep;19(3):387-99
references.pmid: 9730866
references.citation: Cancer Res. 2009 Apr 15;69(8):3451-7
references.pmid: 19351828
references.citation: Oncogene. 2007 Aug 13;26(37):5319-28
references.pmid: 17694075
references.citation: Toxicol Sci. 2002 Oct;69(2):400-8
references.pmid: 12377989
references.citation: Am J Physiol Lung Cell Mol Physiol. 2001 Mar;280(3):L537-46
references.pmid: 11159038
references.citation: Clin Exp Allergy. 2006 Apr;36(4):465-74
references.pmid: 16630151
references.citation: Am J Physiol Lung Cell Mol Physiol. 2005 Feb;288(2):L251-65
references.pmid: 15466252
references.citation: J Immunol. 2002 Sep 1;169(5):2253-63
references.pmid: 12193690
references.citation: Int Arch Allergy Immunol. 2001 Jan-Mar;124(1-3):180-2
references.pmid: 11306962
references.citation: J Immunol. 2002 Feb 15;168(4):1903-10
references.pmid: 11823525
references.citation: Diabetes. 2007 Sep;56(9):2260-73
references.pmid: 17563062
references.citation: Am J Respir Cell Mol Biol. 2000 Aug;23(2):228-33
references.pmid: 10919990