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

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.

Resistin-like molecules: a marker, mediator and therapeutic target for multiple diseases

“…In addition, RELMβ also promotes the expression of the inflammatory factors IL-8 and IL-1β by inducing phosphorylation of p38 MAPK in BECs, which is involved in airway inflammation in chronic obstructive pulmonary disease (COPD) [ 51 ]. After the mice are chronically infected with gastrointestinal (GI) helminth Trichuris muris , the goblet cell-derived RELMβ stimulates TNF-α and IL-6 in macrophages, thereby promoting intestinal inflammation [ 52 ]. The macrophages exposed to RELMβ induce the expression of major histocompatibility complex class II (MHC II) and the secretion of IL-12/23p40, which can increase IFN-γ production by recruiting effector Th1 cells into the inflammatory region [ 52 ].…”

Investigation on the Pathological Mechanism of Frequent Exacerbators With Chronic Obstructive Pulmonary Disease Based on the Characteristics of Respiratory Flora

“…It also confirmed that the expressions of TNF-α and IL-6 were elevated and regulated by the IL-1β pathway. Elevated IL-1β and serum IL-6 expression levels in patients with COPD can activate the IL-1β-system inflammatory axis pathway and pose an increased risk for COPD frequent exacerbators ( 27 , 28 ). The results of this study indicated that after Veillonella parvula treatment, the expressions of IL-1, IL-6, and TNF-α in the cells were elevated markedly, and the expression of p-NF-κB was increased substantially, indicating that Veillonella parvula activated the inflammatory pathway and ultimately destroyed cell viability.…”

Inflammatory Biomarkers in Exhaled Breath Condensate: A Systematic Review

“…Pro-inflammatory Response to exogenous and endogenous noxious stimuli and induction of IL-6 and IL-8 secretion by bronchial epithelial cells [14,15].…”

“…Pro-inflammatory Neutrophil recruitment with an important role in pathological and physiological conditions [15,17].…”