Reddy AT, et al. - Researchers to ascertain the mechanisms involved in lung inflammation triggered by cigarette smoke (CS), the major cause of the chronic obstructive pulmonary disease (COPD). Inflammatory responses are controlled by Nur77, a nuclear hormone receptor belonging to the immediate-early response gene family, mainly by its suppressing action on the NF-κB signaling pathway. Because it is unknown if Nur77’s anti-inflammatory role changes COPD, they examined the influence of Nur77 expression and activity on CS-induced airway inflammation. Downregulation of Nur77 was observed in lung tissues and bronchial epithelial cells from COPD patients. In a murine model of CS-induced airway inflammation, CS increased lung inflammation and also diminished Nur77 activity in wild type mice, whereas lungs of Nur77-deficient mice exhibited excessive CS-induced inflammatory responses. The outcomes in in vitro studies of human airway epithelial cells complemented those in vivo data in mice, collectively conferring that CS induced threonine-phosphorylation of Nur77, which is known to interfere with its anti-inflammatory functions. In brief, the outcomes suggest Nur77 as a significant regulator of CS-induced inflammatory responses and support the potential advantages of Nur77 activation for COPD treatment.