MicroRNA-223 modulates the IL-4-medicated macrophage M2-type polarization to control the progress of sepsis
Abstract
MicroRNAs play a variety of roles in the progress of inflammation. Herein, we investigated the roles of miR-223 in governing macrophage polarization balance in the progress of sepsis. We firstly observed that miR-223 was down-regulated at the early phase and up-regulated at the late phase of sepsis in macrophages; the levels of miR-223 were positively correlated to the ratio of M2 macrophages during sepsis. In miR-223 knockout mice, we observed that miR-223 was dispensable for efficient pro-inflammatory responses, but was required for efficient M2-associated phenotype and function. miR-223 deletion increased clinical scores of sepsis, leading to increased mortality in septic mice. Furthermore, we found that miR-223 expression in M2-type macrophages was controlled by interleukin (IL)-4, but not IL-10; IL-4 antibodies were able to downregulate the levels of miR-223, increased the expression of targeted genes Nfat5 and Rasa1, reduced the ratio of M2 macrophages, resulting in a decreased survival rate in septic mice. Meanwhile, miR-223 deficient macrophages appeared a markedly decreased M2-type polarization when induced by IL-4, but did not affect macrophages skew to M2 phenotype induced by IL-10. Taken together, our results demonstrate that miR-223 acts as an important regulator to modulate IL-4-meditated M2-type polarization of macrophages via targeting to Nfat5 and Rasa1 to control the progress of sepsis.
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The discharge of anti-inflammatory cytokines IL-4 or IL-10 can control the progression of sepsis.
“the discharge of anti-inflammatory cytokines IL-4 [19] or IL-10 [12,20,21] can control the progression of sepsis.”
From The F <sub>1</sub> F <sub>o</sub> -ATP synthase α subunit of <i>Candida albicans</i> induces inflammatory responses by controlling amino acid catabolism (2023) · cites this paper as [19]
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- Authors
- Wang, X., Zhang, H., Guo, R., Li, X., Liu, H., Wang, Z., Du, Q., Tong, D., & Huang, Y.
- Affiliations
- Northwest A&F University (CN)
- Shaanxi University of Chinese Medicine (CN)
- Corresponding author
- Tong, Dewen
- Huang, Yong
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2021-07
- Volume
- 96
- Pages
- 107783
- ISSN
- 1567-5769 (ISSN-L)
- OpenAlex
- W3172094235
- Cited by
- 28
- References
- 40
- Citations by year
- 2026: 3 · 2025: 10 · 2023: 6 · 2022: 8 · 2021: 1
- FWCI
- 1.40
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- International Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fundamental Research Funds for the Central Universities
- Shaanxi Province Key Research and Development Projects
- National Natural Science Foundation of China
- China Postdoctoral Science Foundation
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- miR-223, sepsis, macrophage polarization, M2 macrophages, IL-4, NFAT5, RASA1, microRNA, IL-10, sepsis mortality
- MeSH terms
- Animals, Macrophages, Male, Mice, Inbred C57BL, Peritoneal Cavity, Phagocytosis, Phenotype, Interleukin-4, Mice, Knockout, Sepsis, MicroRNAs, Mice, Bacterial Load
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