Abstract
Club cells are critical in maintaining airway integrity via, in part, secretion of immunomodulatory Club cell 10kd protein (CC10) and xenobiotic detoxification. Aryl hydrocarbon receptor (AhR) is important in xenobiotic metabolism, but its role in Club cell function is unclear. To this end, an AhR ligand, 6-formylindolo[3,2-b]carbazole (FICZ, 10nM) was found to induce, in a ligand and AhR-dependent manner, endoplasmic reticulum stress, phospholipid remodeling, free fatty acid and triglyceride synthesis, leading to perilipin 2-dependent lipid droplet (LD) biogenesis in a Club cell-like cell line, NL20. The increase in LDs was due, in part, to the blockade of adipose triglyceride lipase to LDs, while perilipin 5 facilitated LDs-mitochondria connection, leading to the breakdown of LDs via mitochondrial β-oxidation and acetyl-coA generation. In FICZ-treated cells, increased CC10 secretion and its intracellular association with LDs were noted. Administration of low (0.28ng), medium (1.42ng), and high (7.10ng) doses of FICZ in C57BL/6 mice significantly enhanced lipopolysaccharide (LPS, 0.1μg)-induced airway inflammation, mucin secretion, pro-inflammatory cytokines and CC10 in the bronchoalveolar lavage fluids, as compared to those seen in mice receiving LPS alone, suggesting the importance of AhR signaling in controlling the metabolic homeostasis and functions of Club cells.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.