The Role of Interleukin-23 in the Early Development of Emphysema in HIV1(+) Smokers
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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.
Kuo H, Chen C, Hsu A, Wang Y, Lin C, Hsia N Front Immunol. 2024; 14:1302293.
PMID: 38264654 PMC: 10803449. DOI: 10.3389/fimmu.2023.1302293.
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Kreniske J, Kaner R, Glesby M Expert Rev Respir Med. 2023; 17(10):873-887.
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Chemparathy D, Sil S, Callen S, Chand H, Sopori M, Wyatt T Am J Pathol. 2023; 193(4):380-391.
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Kolloli A, Kumar R, Singh P, Narang A, Kaplan G, Sigal A Commun Biol. 2021; 4(1):1256.
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