Critical regulation of inflammation via class A scavenger receptor

Int J Chron Obstruct Pulmon Dis. 2018 Apr 13:13:1145-1155. doi: 10.2147/COPD.S153326. eCollection 2018.

Abstract

Background: Inflammation is an important cause of COPD. Alveolar macrophages are the major innate immune cells that have an important role in COPD pathology. Class A scavenger receptor (SR-A) is a pattern recognition receptor expressed on macrophages. This study investigates the role of SR-A in COPD progression via regulation of inflammation.

Patients and methods: SR-A expression in COPD patients and control subjects (smokers and nonsmokers without COPD) was measured by immunohistochemistry, immunofluorescence, and real-time PCR. The cytokine levels in BAL were measured by enzyme-linked immunosorbent assay. To further prove our hypothesis, we treated RAW264.7 cells that overexpress SR-A with lipopolysaccharides, poly(I:C), cigarette smoke extract, and H1N1 influenza separated from patients for 24 h and examined the levels of inflammatory cytokines.

Results: In both groups, COPD and smokers without COPD, SR-A expression level was upregulated in alveolar macrophages. SR-A mRNA level was positively correlated with inflammatory cytokines and negatively correlated with FEV1% predicted in COPD patients. In RAW-SR-A cells, level of inflammatory cytokines was significantly higher when compared with control ones.

Conclusion: SR-A could increase inflammation stimulated by cigarette smoke extracts, bacteria, and virus, leading to long-term inflammation in COPD, and thus might be used as a new therapeutic target for COPD treatment.

Keywords: H1N1 influenza; chronic obstructive pulmonary disease; cigarette smoke extract; class A scavenger receptor; inflammation; lipopolysaccharides; poly(I:C).

MeSH terms

  • Aged
  • Animals
  • Case-Control Studies
  • Cytokines / metabolism
  • Female
  • Forced Expiratory Volume
  • Host-Pathogen Interactions
  • Humans
  • Inflammation Mediators / metabolism
  • Influenza A Virus, H1N1 Subtype / immunology
  • Lipopolysaccharides / pharmacology
  • Lung / immunology
  • Lung / metabolism*
  • Lung / physiopathology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / immunology
  • Macrophages, Alveolar / metabolism*
  • Macrophages, Alveolar / virology
  • Male
  • Mice
  • Middle Aged
  • Pneumonia / genetics
  • Pneumonia / immunology
  • Pneumonia / metabolism*
  • Pneumonia / physiopathology
  • Poly I-C / pharmacology
  • Pulmonary Disease, Chronic Obstructive / genetics
  • Pulmonary Disease, Chronic Obstructive / immunology
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • RAW 264.7 Cells
  • Scavenger Receptors, Class A / genetics
  • Scavenger Receptors, Class A / immunology
  • Scavenger Receptors, Class A / metabolism*
  • Signal Transduction
  • Smoke / adverse effects
  • Smoking / adverse effects
  • Up-Regulation

Substances

  • Cytokines
  • Inflammation Mediators
  • Lipopolysaccharides
  • Scavenger Receptors, Class A
  • Smoke
  • lipopolysaccharide, E coli O55-B5
  • Poly I-C