Barjaktarevic Igor Z, Crystal Ronald G, Kaner Robert J
Division of Pulmonary and Critical Care Medicine, Weill Medical College of Cornell University, New York, NY 10065, USA.
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.
J Immunol Res. 2016;2016:3463104. doi: 10.1155/2016/3463104. Epub 2016 Jun 29.
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.
原理。在患肺气肿的HIV1阳性吸烟者的肺泡巨噬细胞（AM）中，基质金属蛋白酶-9（MMP-9）的表达上调。鉴于与HIV1阴性吸烟者相比，HIV1阳性吸烟者的肺上皮衬液（ELF）中炎症细胞因子水平升高，我们推测HIV1阳性吸烟者肺细胞因子的上调可能在功能上与MMP-9表达增加有关。方法。细胞因子阵列评估了从5组个体获得的ELF中的细胞因子蛋白水平：HIV1阴性健康非吸烟者、HIV1阴性健康吸烟者、HIV1阴性低弥散功能（DLCO）吸烟者、HIV1阳性非吸烟者以及HIV1阳性低DLCO吸烟者。结果。在HIV1阴性低DLCO吸烟者以及HIV1阳性吸烟者和非吸烟者中发现Th17相关细胞因子IL-23水平升高。HIV1阳性个体的AM中IL-23基因相对表达增加，在HIV1阳性低DLCO吸烟者的AM中表达更高。体外感染HIV1可诱导正常AM中IL-23表达。体外IL-23刺激AM/淋巴细胞共培养可诱导MMP-9上调。肺T淋巴细胞表达受体IL-23R并与AM相互作用以上调MMP-9。结论。该机制可能导致HIV1阳性吸烟者肺部组织破坏增加，并提示Th17相关炎症可能起作用。
