title: The Role of Interleukin-23 in the Early Development of Emphysema in HIV1(+) Smokers.
abstract: Rationale. Matrix metalloproteinase-9 (MMP-9) expression is upregulated in alveolar macrophages (AM) of HIV1(+) smokers who develop emphysema. Knowing that lung epithelial lining fluid (ELF) of HIV1(+) smokers contains increased levels of inflammatory cytokines compared to HIV1(-) smokers, we hypothesized that upregulation of lung cytokines in HIV1(+) smokers may be functionally related to increased MMP-9 expression. Methods. Cytokine arrays evaluated cytokine protein levels in ELF obtained from 5 groups of individuals: HIV1(-) healthy nonsmokers, HIV1(-) healthy smokers, HIV1(-) smokers with low diffusing capacity (DLCO), HIV1(+) nonsmokers, and HIV1(+) smokers with low DLCO. Results. Increased levels of the Th17 related cytokine IL-23 were found in HIV1(-) smokers with low DLCO and HIV1(+) smokers and nonsmokers. Relative IL-23 gene expression was increased in AM of HIV1(+) individuals, with greater expression in AM of HIV1(+) smokers with low DLCO. Infection with HIV1 in vitro induced IL-23 expression in normal AM. IL-23 stimulation of AM/lymphocyte cocultures in vitro induced upregulation of MMP-9. Lung T lymphocytes express receptor IL-23R and interact with AM in order to upregulate MMP-9. Conclusion. This mechanism may contribute to the increased tissue destruction in the lungs of HIV1(+) smokers and suggests that Th17 related inflammation may play a role.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Igor Z
authors.initials: IZ
authors.lastname: Barjaktarevic
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA; Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Crystal
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA; Department of Genetic Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA.
authors.forename: Robert J
authors.identifier: 0000-0003-0527-576X
authors.initials: RJ
authors.lastname: Kaner
mesh_terms: D000328:Adult; D018920:Coculture Techniques; D016207:Cytokines / Q000378:metabolism; D004646:Emphysema / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D015658:HIV Infections / Q000150:complications* / Q000276:immunology / Q000821:virology; D006679:HIV Seropositivity; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D053759:Interleukin-23 / Q000235:genetics / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology / Q000378:metabolism; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D018123:Receptors, Interleukin / Q000378:metabolism; D012129:Respiratory Function Tests; D020545:Respiratory Mucosa / Q000276:immunology / Q000378:metabolism; D012907:Smoking / Q000009:adverse effects
chemical_list: D016207:Cytokines; C515500:IL23R protein, human; D018836:Inflammation Mediators; D053759:Interleukin-23; D018123:Receptors, Interleukin; D020780:Matrix Metalloproteinase 9