AI Article Synopsis
- The study examines the interaction between calcium-sensing receptor (CaSR) and TRPV4 channels in macrophages and how they affect macrophage polarization through calcium signaling.
- Researchers used peritoneal macrophages from wild-type and TRPV4 knockout mice to analyze the role of these channels and how they respond to lipopolysaccharide (LPS) treatment, measuring various polarization markers.
- Results indicate that CaSR and TRPV4 channels are coupled and play a significant role in promoting M1 macrophage polarization, suggesting potential therapeutic implications for immune-related diseases.
Article Abstract
Aim: Although calcium-sensing receptor (CaSR) and transient receptor potential vanilloid 4 (TRPV4) channels are functionally expressed on macrophages, it is unclear if they work coordinately to mediate macrophage function. The present study investigates whether CaSR couples to TRPV4 channels and mediates macrophage polarization via Ca signaling.
Methods: The role of CaSR/TRPV4/Ca signaling was assessed in lipopolysaccharide (LPS)-treated peritoneal macrophages (PMs) from wild-type (WT) and TRPV4 knockout (TRPV4 KO) mice. The expression and function of CaSR and TRPV4 in PMs were analyzed by immunofluorescence and digital Ca imaging. The correlation factors of M1 polarization, CCR7, IL-1β, and TNFα were detected using q-PCR, western blot, and ELISA.
Results: We found that PMs expressed CaSR and TRPV4, and CaSR activation-induced marked Ca signaling predominately through extracellular Ca entry, which was inhibited by selective pharmacological blockers of CaSR and TRPV4 channels. The CaSR activation-induced Ca signaling was significantly attenuated in PMs from TRPV4 KO mice compared to those from WT mice. Moreover, the CaSR activation-induced Ca entry via TRPV4 channels was inhibited by blocking phospholipases A2 (PLA2)/cytochromeP450 (CYP450) and phospholipase C (PLC)/Protein kinase C (PKC) pathways. Finally, CaSR activation promoted the expression and release of M1-associated cytokines IL-1β and TNFɑ, which were attenuated in PMs from TRPV4 KO mice.
Conclusion: We reveal a novel coupling of the CaSR and TRPV4 channels via PLA2/CYP450 and PLC/PKC pathways, promoting a Ca -dependent M1 macrophage polarization. Modulation of this coupling and downstream pathways may become a potential strategy for the prevention/treatment of immune-related disease.
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| http://dx.doi.org/10.1111/apha.13926 | DOI Listing |
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