Myosin 1F Regulates M1-Polarization by Stimulating Intercellular Adhesion in Macrophages
| Autor: | Leopoldo Santos-Argumedo, José L. Maravillas-Montero, Zayda L. Piedra-Quintero, Porfirio Nava, Mineko Shibayama, Nicolás Villegas-Sepúlveda, Oscar Medina-Contreras, Sandra Romero-Ramírez, Carolina Serrano |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine lcsh:Immunologic diseases. Allergy M1-polarization Interleukin-1beta Primary Cell Culture Immunology Macrophage polarization myosin 1F Inflammation Proinflammatory cytokine Epithelial Damage Mice Myosin Type I 03 medical and health sciences 0302 clinical medicine Cell Line Tumor Myosin medicine Akt/mTOR/STAT signaling Animals Humans Immunology and Allergy Secretion Protein kinase B Cytoskeleton PI3K/AKT/mTOR pathway Original Research Mice Knockout Chemistry Macrophages Dextran Sulfate Macrophage Activation Integrin alphaVbeta3 Cell biology Mice Inbred C57BL intercellular adhesion Disease Models Animal RAW 264.7 Cells 030104 developmental biology inflammation Colitis Ulcerative medicine.symptom lcsh:RC581-607 030215 immunology |
| Zdroj: | Frontiers in Immunology, Vol 9 (2019) Frontiers in Immunology |
| ISSN: | 1664-3224 |
| DOI: | 10.3389/fimmu.2018.03118/full |
| Popis: | Intestinal macrophages are highly mobile cells with extraordinary plasticity and actively contribute to cytokine-mediated epithelial cell damage. The mechanisms triggering macrophage polarization into a proinflammatory phenotype are unknown. Here, we report that during inflammation macrophages enhance its intercellular adhesion properties in order to acquire a M1-phenotype. Using in vitro and in vivo models we demonstrate that intercellular adhesion is mediated by integrin-alphaVbeta3 and relies in the presence of the unconventional class I myosin 1F (Myo1F). Intercellular adhesion mediated by alphaVbeta3 stimulates M1-like phenotype in macrophages through hyperactivation of STAT1 and STAT3 downstream of ILK/Akt/mTOR signaling. Inhibition of integrin-alphaVbeta3, Akt/mTOR or lack of Myo1F attenuated the commitment of macrophages into a pro-inflammatory phenotype. In a model of colitis, Myo1F deficiency strongly reduces the secretion of proinflammatory cytokines, decreases epithelial damage, ameliorates disease activity and enhances tissue repair. Together our findings uncover an unknown role for Myo1F as part of the machinery that regulates intercellular adhesion and polarization in macrophages. |
| Databáze: | OpenAIRE |
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