Journal
MOLECULAR IMMUNOLOGY
Volume 107, Issue -, Pages 1-9Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.molimm.2018.12.027
Keywords
IL-16; mir-145-3p; Macrophage; Polarization; M1/M2
Categories
Funding
- Yunnan Science and Technology Department [2013FZ269, 2014FB025, 2018FE001(-33)]
- Kunming Medical University Foundation [2013FZ269, 2014FB025, 2018FE001(-33)]
- Scientific Research Projects of Research Institutes in Yunnan Medical and Health Units [2015NS024, 2016BS016, 2016NS022, 2017NS024, 2017NS048, 2018NS0104]
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Background: Interleukin 16 is an immunomodulatory chemokine that signals through CD4 + T cells, monocytes, macrophages and dendritic cells. Its expression in immune-related cells enhances the antimicrobial effect and inhibits HIV replication in macrophages. However, the role of IL-16 in macrophage polarization is uncertain. Mir-145 was reported to regulate IL-10 expression by targeting histone deacetylase 11 and promotes alternatively activated macrophage (M2) polarization. Mir-145 was also predicted to target IL-16 mRNA. We aimed to explore the roles of IL-16 and mir-145 in macrophage polarization and antimicrobial functions. Methods: THP1 monocytes were employed in this study, and their cell activity when incubated with different concentrations of IL-16 was evaluated using the CCK-8 cell counting kit. To obtain polarized macrophages, THP1 cells were induced by IL-4 and IL-13 following PMA incubation (M2 polarized macrophages) or induced by IFN-gamma and LPS (M1 classical macrophage activation). The influence of IL-16 on macrophage phagocytosis was quantified by the amount of chicken red blood cell phagocytized. IL-16, IL-10 and miR-145 expression in THP1 monocytes and induced macrophages was quantified by quantitative PCR. The miR-145 and IL-16 targeting relationship was verified by the dual luciferase reporter assay. The influence of IL-16 and mir-145 on macrophage polarization was evaluated by M1 and M2 macrophage characterized marker gene expression. Results: The MO macrophage subtype was induced by PMA. The M1 and M2 subtypes of macrophage were successfully induced by M1- and M2-specific induction. M1 macrophages express higher levels of IL-16 than M2 macrophages but express lower levels of IL-10 and mir-145 than M2 cells. IL-16 with a concentration up to 150 ng/mL has no influence on THP-1 cell proliferation but improves macrophage phagocytosis ability with the down-expression of IL-10 and up-expression of pro-inflammatory cytokines such as IL-1a and IL-6. Knockdown with its target siRNA is beneficial for macrophage maintenance but reduces phagocytosis ability. Mir-145 specifically targets the IL-16 3'UTR verified by the dual luciferase reporter assay. Mir-145 downregulates IL-16 expression and upregulates IL-10 expression, thereby promoting M2 macrophage polarization. Conclusion: IL-16 modulates macrophage polarization through regulating IL-10, IL-1a and IL-6 expression. Mir 145 is involved in M2 macrophage polarization by targeting IL-16 and enhancing IL-10 expression.
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