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Calcitonin gene-related peptide exerts anti-inflammatory property through regulating murine macrophages polarization in vitro.
- Source :
-
Molecular immunology [Mol Immunol] 2017 Nov; Vol. 91, pp. 105-113. Date of Electronic Publication: 2017 Sep 08. - Publication Year :
- 2017
-
Abstract
- Acute lung injury (ALI) is a condition resulting from direct or indirect lung injury associated with high mortality and morbidity. The phenotype of macrophages in lung contributes to the pathological progress of ALI. Calcitonin gene-related peptide (CGRP) is one of the most abundant neuropeptides in lung, and attenuates lipopolysaccharide (LPS)-induced ALI in rats. However, the exact effect of CGRP on the activation of macrophages remains unknown. Here we investigate the effect of CGRP on the macrophages activation and inflammation in murine macrophages in vitro. We found that LPS increased the expression of CGRP in a LPS-induced ALI murine model and LPS-stimulated murine macrophages. Although CGRP didn't alter the expression of tumor necrosis factor-α (a marker of pro-inflammatory phenotype of macrophages, M1 macrophages) or Arginase 1 (Arg1, a marker of M2 macrophages) in non-differentiated macrophages, CGRP significantly reduced the NLRP3 and pro-IL-1β mRNA expression induced by LPS, as well as NLRP3 protein and IL-1β secretion induced by LPS+ATP in macrophages in vitro. On the other hand, CGRP dramatically enhanced the Arg1 expression and activity induced by IL-4 in the time- and dose-dependent manners. CGRP also promoted the expression of markers of M2 macrophages (IL-10, Fizz1 and Mrc1) induced by IL-4 in murine macrophages. These effects of CGRP were also observed in primary murine peritoneal macrophages. In addition, we found that CGRP regulated macrophages polarization partially through calmodulin, PKC and PKA pathways. Specifically, CGRP could inhibit the degradation of I-κB induced by LPS, and enhance the phosphorylation of STAT6 induced by IL-4 in macrophages. In conclusion, our results indicate that CGRP regulates macrophage polarization and inhibits inflammation in murine macrophages.<br /> (Copyright © 2017 Elsevier Ltd. All rights reserved.)
- Subjects :
- Acute Lung Injury chemically induced
Acute Lung Injury pathology
Animals
Antigens, Differentiation immunology
Cytokines immunology
Disease Models, Animal
I-kappa B Proteins immunology
Lipopolysaccharides toxicity
Macrophages pathology
Male
Mice
Rats
STAT6 Transcription Factor immunology
Acute Lung Injury immunology
Calcitonin Gene-Related Peptide immunology
Macrophages immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1872-9142
- Volume :
- 91
- Database :
- MEDLINE
- Journal :
- Molecular immunology
- Publication Type :
- Academic Journal
- Accession number :
- 28892747
- Full Text :
- https://doi.org/10.1016/j.molimm.2017.08.020