| First Author | Sundar IK | Year | 2017 |
| Journal | Biochem Biophys Res Commun | Volume | 493 |
| Issue | 4 | Pages | 1390-1395 |
| PubMed ID | 28974420 | Mgi Jnum | J:251172 |
| Mgi Id | MGI:6103757 | Doi | 10.1016/j.bbrc.2017.09.157 |
| Citation | Sundar IK, et al. (2017) The nuclear receptor and clock gene REV-ERBalpha regulates cigarette smoke-induced lung inflammation. Biochem Biophys Res Commun 493(4):1390-1395 |
| abstractText | REV-ERBalpha is a nuclear heme receptor, transcriptional repressor and critical component of the molecular clock that drives daily rhythms of metabolism. Evidence reveals that REV-ERBalpha also plays an important regulatory role in clock-dependent lung physiology and inflammatory responses. We hypothesize that cigarette smoke (CS) exposure influences REV-ERBalpha abundance in the lungs, facilitating a pro-inflammatory phenotype. To determine the impact of REV-ERBalpha activation in the CS-induced inflammatory response we treated primary human small airway epithelial cells (SAECs) with CS extract (CSE) or lipopolysaccharide (LPS) in the absence or presence of pre-treatment with the REV-ERBalpha agonist GSK 4112. We also exposed adult C57BL/6J (WT) and Rev-erbalpha global KO mice to CS (10 and 30 days) and measured pro-inflammatory cytokine release. Our data reveal that pre-treatment with GSK 4112 reduced CSE/LPS induced pro-inflammatory cytokines release from both SAECs and mouse lung fibroblasts (MLFs). Furthermore, REV-ERBalpha KO mice show a greater inflammatory response to 10 and 30 days of CS, including increased neutrophil lung influx, pro-inflammatory cytokine (IL-6, MCP-1 and KC) release, and pro-senescence marker (p16) when compared to WT mice. These data demonstrate that REV-ERBalpha is a critical regulator of CS-induced lung inflammatory responses. |
