The Role of Interleukin-23 in the Early Development of Emphysema in HIV1(+) Smokers.

Publication TypeJournal Article
Year of Publication2016
AuthorsBarjaktarevic IZ, Crystal RG, Kaner RJ
JournalJ Immunol Res
Date Published2016
KeywordsAdult, Coculture Techniques, Cytokines, Emphysema, Female, Gene Expression, HIV Infections, HIV Seropositivity, Humans, Inflammation Mediators, Interleukin-23, Lymphocytes, Macrophages, Alveolar, Male, Matrix Metalloproteinase 9, Middle Aged, Receptors, Interleukin, Respiratory Function Tests, Respiratory Mucosa, Smoking

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.

Alternate JournalJ Immunol Res
PubMed ID27446965
PubMed Central IDPMC4942665
Grant ListP50 HL084936 / HL / NHLBI NIH HHS / United States
R01 HL118857 / HL / NHLBI NIH HHS / United States
UL1 TR000457 / TR / NCATS NIH HHS / United States