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Das, A., Ganesh, K., & Khanna, S. (2014). Engulfment of Apoptotic Cells by Macrophages: A Role of MicroRNA-21 in the Resolution of Wound Inflammation. The Journal of Immunology, 192(3), 1120–1129. Added by: Dr. Enrique Feoli (13/08/2023, 16:34) Last edited by: Dr. Enrique Feoli (13/08/2023, 16:35) |
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| Resource type: Journal Article DOI: 10.4049/jimmunol.1300613 ID no. (ISBN etc.): 0022-1767 BibTeX citation key: Das2014 View all bibliographic details  |
Categories: BioAcyl Corp Subcategories: Efferocytosis Creators: Das, Ganesh, Khanna Collection: The Journal of Immunology |
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| Abstract |
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{At an injury site, efficient clearance of apoptotic cells by wound macrophages or efferocytosis is a prerequisite for the timely resolution of inflammation. Emerging evidence indicates that microRNA-21 (miR-21) may regulate the inflammatory response. In this work, we sought to elucidate the significance of miR-21 in the regulation of efferocytosis-mediated suppression of innate immune response, a key process implicated in resolving inflammation following injury. An increased expression of inducible miR-21 was noted in postefferocytotic peripheral blood monocyte-derived macrophages. Such induction of miR-21 was associated with silencing of its target genes PTEN and PDCD4. Successful efferocytosis of apoptotic cells by monocyte-derived macrophages resulted in the suppression of LPS-induced NF-κB activation and TNF-α expression. Interestingly, bolstering of miR-21 levels alone, using miR mimic, resulted in significant suppression of LPS-induced TNF-α expression and NF-κB activation. We report that efferocytosis-induced miR-21, by silencing PTEN and GSK3β, tempers the LPS-induced inflammatory response. Macrophage efferocytosis is known to trigger the release of anti-inflammatory cytokine IL-10. This study demonstrates that following successful efferocytosis, miR-21 induction in macrophages silences PDCD4, favoring c-Jun–AP-1 activity, which in turn results in elevated production of anti-inflammatory IL-10. In summary, this work provides direct evidence implicating miRNA in the process of turning on an anti-inflammatory phenotype in the postefferocytotic macrophage. Elevated macrophage miR-21 promotes efferocytosis and silences target genes PTEN and PDCD4, which in turn accounts for a net anti-inflammatory phenotype. Findings of this study highlight the significance of miRs in the resolution of wound inflammation.}
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