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

Overview

MeSH

  • Adult
  • Coculture Techniques
  • Cytokines
  • Female
  • Gene Expression
  • HIV Seropositivity
  • Humans
  • Inflammation Mediators
  • Lymphocytes
  • Macrophages, Alveolar
  • Male
  • Matrix Metalloproteinase 9
  • Middle Aged
  • Receptors, Interleukin
  • Respiratory Function Tests
  • Respiratory Mucosa

MeSH Major

  • Emphysema
  • HIV Infections
  • Interleukin-23
  • Smoking

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.

publication date

  • 2016

has subject area

  • Adult
  • 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

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4942665

Digital Object Identifier (DOI)

  • 10.1155/2016/3463104

PubMed ID

  • 27446965

Additional Document Info

start page

  • 3463104

volume

  • 2016