The Inflammatory Response Induced by RELMβ Upregulates IL-8 and IL-1β Expression in Bronchial Epithelial Cells in COPD

Int J Chron Obstruct Pulmon Dis. 2021 Sep 2:16:2503-2513. doi: 10.2147/COPD.S321877. eCollection 2021.

Abstract

Purpose: Chronic obstructive pulmonary disease (COPD) is associated with a complex inflammatory regulatory network. Resistin-like molecule β (RELMβ) is highly expressed in the lungs of COPD patients. We aimed to investigate the proinflammatory effect of RELMβ on airway epithelial cells in COPD.

Methods: First, a GEO dataset was used to analyze the expression of the RELMβ gene in the COPD and control groups as well as the protein levels of RELMβ in the sera of outpatients with COPD and normal control subjects in our hospital. We also stimulated 16HBE bronchial epithelial cells with recombinant RELMβ protein and analyzed the expression of IL-8 and IL-1β. We upregulated and downregulated the gene expression of RELMβ in 16HBE cells and analyzed the expression of the inflammatory cytokines IL-8 and IL-1β. In addition, we also examined the mechanism by which the p38 MAPK signaling pathway contributed to the regulation of IL-8 and IL-1β expression by RELMβ.

Results: RELMβ expression was increased in COPD tissues in different data sets and in the serum of COPD patients in our hospital. IL-8 and IL-1β expression was also increased in COPD tissues with high RELMβ gene expression in different data sets. The RELMβ gene was mainly related to inflammatory factors and inflammatory signaling pathways in the PPI regulatory network. Experiments at the cellular level showed that RELMβ promoted the expression of the inflammatory cytokines IL-8 and IL-1β, and this regulation was mediated by the p38 MAPK signaling pathway.

Conclusion: RELMβ can promote the expression of the inflammatory cytokines IL-8 and IL-1β in bronchial epithelial cells of patients with COPD and exert inflammatory effects. RELMβ may be a potential target for the treatment of COPD.

Keywords: IL-1β; IL-8; chronic obstructive pulmonary disease; p38 MAPK; resistin-like molecule beta/RELMβ.

MeSH terms

  • Cytokines
  • Epithelial Cells
  • Humans
  • Interleukin-8* / genetics
  • Pulmonary Disease, Chronic Obstructive* / genetics
  • Signal Transduction

Substances

  • Cytokines
  • Interleukin-8