ERS Respiratory Channel

CDN Connection Issue

It appears that your current network does not allow connection to the CDN (Content Delivery Network) required for this service to function properly.

To resolve this issue, please try the following actions :

• Contact your network administrator : Inform them of this restriction so they can adjust the network settings accordingly.

• Use another network : Try connecting from a different network, such as another Wi-Fi network or a mobile connection.

We apologize for the inconvenience and thank you for your understanding.

Abstract

Background

REV-ERB? (NR1D1) is a crucial clock gene that is decreased in smokers and COPD patients compared to nonsmokers. Depletion of Nr1d1 aggravated CS-induced airway epithelial inflammation. Distinct macrophage polarization phenotypes exhibit diverse functions, the disordered polarization of M1-like (pro-inflammatory) and M2-like (anti-inflammatory) phenotype plays a crucial role in CS-induced airway inflammation. However, the regulatory role of NR1D1 in CS-induced polarization of macrophages remains unclear.

Methods

Bone marrow-derived macrophages (BMDM) from wild-type (WT) and Nr1d1 knockout (Nr1d1^-/^-) mice were stimulated with CS extract (CSE). WT and Nr1d1^-^/- mice were exposed to CS for 10 days. Cytokines related to M1 (iNOS, IL-1?, and CXCL2) and M2 phenotype (IL-10) in cells and bronchoalveolar lavage fluid (BALF) of mice were measured by RT-PCR/Western Blot and Luminex assay, respectively. Proportion of M1(CD86⁺IL-10^?)and M2 phenotype (CD86^?IL-10⁺) in lung homogenate (LH) was assessed by Flow cytometry.

Results

We observed upregulation of both cytokines and proportion of M1 and M2 phenotype in CSE-treated WT BMDM and BALF/LH of CS-exposed WT mice (all p<0.05). Nr1d1 knockout further increased M1-related markers, but decreased M2-related marker in both in vitro and in vivo experiments (all p<0.05). After CS exposure, proportion of M2 phenotype in LH was downregulated in Nr1d1^-^/- mice compared to WT mice (p<0.05), while no significant change was observed in M1-phenotype.

Conclusion

Nr1d1 knockout promotes M1 macrophage polarization while inhibits M2 polarization in CS-induced airway inflammation. Targeting NR1D1 in macrophage may provide a novel therapeutic approach for CS-related airway inflammation.

Abstract

#{title}