Metabolic regulation of the circadian clock in classically and alternatively activated macrophages

0571585 - FGÚ 2024 RIV US eng J - Journal Article
Honzlová, Petra - Sumová, Alena
Metabolic regulation of the circadian clock in classically and alternatively activated macrophages.
Immunology and Cell Biology. Roč. 101, č. 5 (2023), s. 428-443. ISSN 0818-9641. E-ISSN 1440-1711
Research Infrastructure: Czech-BioImaging II - 90129
Institutional support: RVO:67985823
Keywords : circadian clock * gw9662 * macrophage * polarization * PPAR gamma * rosiglitazone
OECD category: Physiology (including cytology)
Impact factor: 4, year: 2022
Method of publishing: Limited access
https://doi.org/10.1111/imcb.12640

Macrophages exhibit a range of functional pro- and anti-inflammatory states that induce changes in their cellular metabolism. We aimed to elucidate whether these changes affect the molecular properties of their circadian clock focusing on their anti-inflammatory phenotype. Primary cell cultures of bone marrow-derived macrophages (BMDMs, nonpolarized M0 BMDM) from PER2::LUC (fusion protein of PERIOD2 and LUCIFERASE) mice were polarized into the M1 (proinflammatory) or M2 (anti-inflammatory) phenotype, and PER2-driven bioluminescence was recorded in real-time at the cell-population and single-cell levels. Viability, clock gene expression profiles, polarization plasticity and peroxisome proliferator-activated receptor ? (PPAR?) protein levels were analyzed. The effects of pharmacological activation/inhibition of PPAR? (rosiglitazone/GW9662) and inhibition of fatty acid oxidation (FAO) by etomoxir in M2 BMDM cell cultures were examined. The parameters of PER2-driven bioluminescence rhythms differed between M0, M1 and M2 BMDM cultures at cell-population and single-cell levels. Compared with M0, polarization to M2 did not change the period but increased amplitude, mean bioluminescence level and rhythm persistence. Polarization to M1 shortened the period but had no effect on the amplitude of the rhythm. The same period changes were observed after a bidirectional switch between M1- and M2-polarized states in the same culture. Both PPAR? activation/inhibition and FAO inhibition modulated the clock in M2 BMDMs, suggesting metabolic regulation of the M2 clock. Our results indicate that bidirectional changes in the properties of BMDM circadian clocks in response to their actual polarization are mediated via changes in their metabolic state. They provide new information on the interrelationship between the BMDM polarization, their circadian clock and cellular metabolism.
Permanent Link: https://hdl.handle.net/11104/0342759