LincR-PPP2R5C regulates IL-1β ubiquitination in macrophages and promotes airway inflammation and emphysema in a murine model of COPD.

Chronic obstructive pulmonary disease (COPD) is a common disease with high global morbidity and mortality. Macrophages release IL-1β and orchestrate airway inflammation in COPD. Previously, we explored the role of a new lncRNA, LincR-PPP2R5C, in regulating Th2 cells in asthma. Here, we established a murine model of COPD and explored the roles and mechanisms by which LincR-PPP2R5C regulates IL-1β in macrophages. LincR-PPP2R5C was highly expressed in pulmonary macrophages from COPD-like mice. LincR-PPP2R5C deficiency ameliorated emphysema and pulmonary inflammation, as characterized by reduced IL-1β in macrophages. Unexpectedly, in both lung tissues and macrophages, LincR-PPP2R5C deficiency decreased the expression of the IL-1β protein but not the IL-1β mRNA. Furthermore, we found that LincR-PPP2R5C deficiency increased the level of ubiquitinated IL-1β in macrophages, which was mediated by PP2A activity. Targeting PP2A with FTY720 decreased IL-1β and improved COPD. In conclusion, LincR-PPP2R5C regulates IL-1β ubiquitination by affecting PP2A activity in macrophages, contributing to the airway inflammation and emphysema in a murine model of COPD. PP2A and IL-1β ubiquitination in macrophages might be new therapeutic avenues for COPD therapy.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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