Glucagon-like peptide-1 receptor (GLP-1R) signaling ameliorates dysfunctional immunity in COPD patients.

Int J Chron Obstruct Pulmon Dis

Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China,

Published: March 2019

Background: The glucagon-like peptide-1 receptor (GLP-1R) agonist - liraglutide (LIR) - is an insulin secretagogue for the treatment of diabetes and has been proven to have therapeutic potential in the treatment of COPD. Evidence suggested that activating GLP-1R signaling might have immunomodulating and anti-inflammatory effects. COPD is characterized by dysregulation of immunity, oxidative stress, and excessive inflammation responses. The aim of this study was to investigate whether GLP-1R signaling had a regulatory role in COPD immunity.

Patients And Methods: Fifty-seven COPD patients in a stable condition and 51 age-, sex-, and smoking history-matched non-COPD subjects provided blood samples for isolation of peripheral blood mononuclear cells (PBMCs). GLP-1R expression was measured, and its association with clinical parameters and plasma cytokines was analyzed. T cell function was assessed at baseline and after regulating GLP-1R expression.

Results: GLP-1R expression decreased in circulating PBMCs of COPD patients, which was associated with decreased interferon (IFN)-γ expression. Reduced IFN-γ production stimulated by phytohemagglutinin (PHA) and increased programmed cell death protein 1 (PD-1) expression on T cells were observed in COPD patients compared with non-COPD subjects. Treatment with LIR could upregulate the GLP-1R expression, and this was observed to restore the antigen-stimulated IFN-γ production and downregulate PD-1 expression in T cells.

Conclusion: PBMCs of COPD patients showed defective GLP-1R signaling and functional T-lymphocyte abnormalities that could be rescued by LIR treatment.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6186765PMC
http://dx.doi.org/10.2147/COPD.S175145DOI Listing

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