Increased IL-33 expression in chronic obstructive pulmonary disease

Am J Physiol Lung Cell Mol Physiol. 2015 Apr 1;308(7):L619-27. doi: 10.1152/ajplung.00305.2014. Epub 2015 Jan 16.

Abstract

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by inflammatory cell activation and the release of inflammatory mediators. Interleukin-33 (IL-33) plays a critical role in various inflammatory and immunological pathologies, but evidence for its role in COPD is lacking. This study aimed to investigate the expression of IL-33 in COPD and to determine whether IL-33 participates in the initiation and progression of COPD. Levels of serum IL-33 and its receptors were measured by ELISA, and serum levels of IL-33, ST2, and IL-1 receptor accessory protein were elevated in patients with COPD compared with control subjects. Flow cytometry analysis further demonstrated an increase in peripheral blood lymphocytes (PBLs) expressing IL-33 in patients with COPD. Immunofluorescence analysis revealed that the main cellular source of IL-33 in lung tissue was human bronchial epithelial cells (HBEs). Cigarette smoke extract and lipopolysaccharide could enhance the ability of PBLs and HBEs to express IL-33. Furthermore, PBLs from patients with COPD showed greater IL-33 release in response to the stimulus. Collectively, these findings suggest that IL-33 expression levels are increased in COPD and related to airway and systemic inflammation. Therefore, IL-33 might contribute to the pathogenesis and progression of this disease.

Keywords: chronic obstructive pulmonary disease; human bronchial epithelial cells; interleukin-33; peripheral blood lymphocytes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Cells, Cultured
  • Female
  • Genetic Association Studies
  • Humans
  • Interleukin-1 Receptor Accessory Protein / blood
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins / blood*
  • Interleukins / genetics
  • Lipopolysaccharides / pharmacology
  • Lung / metabolism
  • Lymphocytes / immunology
  • Lymphocytes / metabolism
  • Male
  • Middle Aged
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Polymorphism, Single Nucleotide
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Receptors, Cell Surface / blood
  • Toll-Like Receptor 4 / genetics
  • Up-Regulation

Substances

  • IL1RAP protein, human
  • IL1RL1 protein, human
  • IL33 protein, human
  • Interleukin-1 Receptor Accessory Protein
  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33
  • Interleukins
  • Lipopolysaccharides
  • Receptors, Cell Surface
  • TLR4 protein, human
  • Toll-Like Receptor 4