LXRα agonist differentially regulates BAFF expression and biological effects in RAW264.7 cells depending on growth status: LXRα activation and BAFF signaling in RAW264.7 cells.

Autor: Teng Y; Urology Department, Third Affiliated Hospital of Soochow University, Changzhou, China., Xu H; Urology Department, Third Affiliated Hospital of Soochow University, Changzhou, China. Electronic address: xuhaiyan09@163.com., He X; Urology Department, Third Affiliated Hospital of Soochow University, Changzhou, China., Zhuang Q; Urology Department, Third Affiliated Hospital of Soochow University, Changzhou, China., Lu H; Urology Department, Third Affiliated Hospital of Soochow University, Changzhou, China., Xu R; Urology Department, Third Affiliated Hospital of Soochow University, Changzhou, China., Xue D; Urology Department, Third Affiliated Hospital of Soochow University, Changzhou, China.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2025 Jan; Vol. 742, pp. 151067. Date of Electronic Publication: 2024 Nov 30.
DOI: 10.1016/j.bbrc.2024.151067
Abstrakt: B- cell-activating factor (BAFF), which is essential for the survival and development of B cells, is mainly produced by myeloid cells such as macrophages. Abnormal macrophage infiltration and high BAFF expression in kidney allografts are associated with the occurrence and development of antibody-mediated rejection (ABMR). Nuclear hormone receptor Liver X receptors (LXRs), is a nonnegligible participant in regulating cholesterol metabolism and inflammatory responses. Nowadays the effects of LXRα activation on macrophages have been widely studied, however the effects of LXRα activation on BAFF expression and cell function due to the change of BAFF signaling have not yet been fully investigated. In the present study, LXRα activation alone was found to downregulate BAFF expression in quiescent RAW 264.7 cells, whereas LXRα agonist significantly upregulated BAFF expression in cells pretreated with lipopolysaccharide (LPS) for 6 h. The increased BAFF signaling promoted M1 polarization and enhanced cell viability, migration, and phagocytic ability. LXRα can directly bind to the BAFF promoter region and decrease BAFF expression in RAW264.7 cells. LXRα activation enhanced mitochondrial metabolism, which promoted BAFF expression in the LPS-activated cells. Our results indicate that subtle changes in the microenvironment would affect the biological function of macrophages, in which a variety of BAFF signaling pathways may also be involved, providing a new perspective on exploring the mechanism of allograft rejection and uncovering the potential reason for the unstable efficacy of anti-BAFF preparations in kidney transplant recipients.
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.
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE