| First Author | Nascimento Da Conceicao V | Year | 2021 |
| Journal | iScience | Volume | 24 |
| Issue | 11 | Pages | 103339 |
| PubMed ID | 34816101 | Mgi Jnum | J:328768 |
| Mgi Id | MGI:6833967 | Doi | 10.1016/j.isci.2021.103339 |
| Citation | Nascimento Da Conceicao V, et al. (2021) Resolving macrophage polarization through distinct Ca(2+) entry channel that maintains intracellular signaling and mitochondrial bioenergetics. iScience 24(11):103339 |
| abstractText | Transformation of naive macrophages into classically (M1) or alternatively (M2) activated macrophages regulates the inflammatory response. Here, we identified that distinct Ca(2+) entry channels determine the IFNgamma-induced M1 or IL-4-induced M2 transition. Naive or M2 macrophages exhibit a robust Ca(2+) entry that was dependent on Orai1 channels, whereas the M1 phenotype showed a non-selective TRPC1 current. Blockade of Ca(2+) entry suppresses pNF-kappaB/pJNK/STAT1 or STAT6 signaling events and consequently lowers cytokine production that is essential for M1 or M2 functions. Of importance, LPS stimulation shifted M2 cells from Orai1 toward TRPC1-mediated Ca(2+) entry and TRPC1(-/-) mice exhibited transcriptional changes that suppress pro-inflammatory cytokines. In contrast, Orai1(-/-) macrophages showed a decrease in anti-inflammatory cytokines and exhibited a suppression of mitochondrial oxygen consumption rate and inhibited mitochondrial shape transition specifically in the M2 cells. Finally, alterations in TRPC1 or Orai1 expression determine macrophage polarization suggesting a distinct role of Ca(2+) channels in modulating macrophage transformation. |
