LincRNA-Cox2 Regulates Smoke-induced Inflammation in Murine Macrophages

Cigarette smoke (CS) exposure is a risk factor for many chronic diseases, including chronic obstructive pulmonary disease, but the mechanism by which smoke exposure can alter homeostasis and bring about chronic inflammation is poorly understood. Here, we showcase a novel role for smoke in regulating long noncoding RNAs, showing that it activates lincRNA-Cox2, which we previously characterized as functional in inflammatory regulation. Exposing lincRNA-Cox2 murine models to smoke in vivo confirmed lincRNA-Cox2 as a regulator of inflammatory gene expression in response to smoke both systemically and within the lung. We also report that lincRNA-Cox2 negatively regulates genes in smoked bone marrow-derived macrophages exposed to LPS stimulation. In addition to the effects on long noncoding RNAs, we also report dysregulated transcription and splicing of inflammatory proteincoding genes in the bone marrow niche after CS exposure in vivo. Collectively, this work provides insights into how innate immune signaling from gene expression to splicing is altered after in vivo exposure to CS and highlights an important new role for lincRNA-Cox2 in regulating immune genes after smoke exposure.

Automated summary

Cigarette smoke exposure is a risk factor for chronic diseases, but the mechanism behind chronic inflammation caused by smoke is not well understood. This study reveals that smoke can activate lincRNA-Cox2, a long noncoding RNA that regulates inflammatory gene expression. It also demonstrates dysregulated gene transcription and splicing in the bone marrow niche after smoke exposure. This work provides insights into the immune signaling alterations caused by cigarette smoke and highlights the important role of lincRNA-Cox2 in regulating immune genes after smoke exposure.