Abstract
BackgroundMicroglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system. Similar to macrophages, microglia adopt two different activation phenotypes, the classical and alternative activation. Resolvin D1 (RvD1) is considered to display potent anti-inflammatory and pro-resolving actions in inflammatory models. In this present study, we investigate the effect of RvD1 on IL-4-induced alternative activation in murine BV-2 microglial cells.MethodsBV-2 cells were incubated with RvD1 alone, IL-4 alone, or the combination of RvD1 and IL-4. Western blot and immunofluorescence were performed to detect protein levels of alternative activation markers arginase 1 (Arg1), chitinase 3-like 3 (Ym1). Moreover, we investigated the effects of RvD1 on IL-4-induced activation of signal transducer and activators of transcription 6 (STAT6) and peroxisome proliferator-activated receptor gamma (PPARγ).ResultsRvD1 promoted IL-4-induced microglia alternative activation by increasing the expression of Arg1 and Ym1. RvD1 also enhanced phosphorylation of STAT6, nuclear translocation of PPARγ and the DNA binding activity of STAT6 and PPARγ. These effects were reversed by butyloxycarbonyl-Phe-Leu-Phe-Leu-Phe (a formyl peptide receptor 2 antagonist). Further, the effects of RvD1 and IL-4 on Arg1 and Ym1 were blocked by the application of leflunomide (a STAT6 inhibitor) or GW9662 (a PPARγ antagonist).ConclusionsOur studies demonstrate that RvD1 promotes IL-4-induced alternative activation via STAT6 and PPARγ signaling pathways in microglia. These findings suggest that RvD1 may have therapeutic potential for neuroinflammatory diseases.
Highlights
Microglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system
BV-2 cells were treated with vehicle (0.038% ethanol) or different concentrations of Resolvin D1 (RvD1) (1 nM, 10 nM and 100 nM) for 30 minutes in the absence or presence of Boc-2 (10 μM), and stimulated by IL-4 (10 ng/ml) for 24 hours. (A, B) The expression of arginase 1 (Arg1) and chitinase 3-like 3 (Ym1) proteins was assessed by Western blot
RvD1 promotes IL-4-induced alternative activation of BV-2 microglial cells Initially, we evaluated the effects of RvD1 on IL-4induced microglia alternative activation; BV-2 cells were treated with vehicle or different concentrations of RvD1 (1 nM, 10 nM and 100 nM) for 30 minutes and stimulated with IL-4 (10 ng/ml) for 24 hours
Summary
Microglia play key roles in innate immunity, homeostasis, and neurotropic support in the central nervous system. Resolvin D1 (RvD1) is considered to display potent anti-inflammatory and pro-resolving actions in inflammatory models. In this present study, we investigate the effect of RvD1 on IL-4-induced alternative activation in murine BV-2 microglial cells. Microglia are considered to be the resident immune cells of the central nervous system (CNS). It is becoming increasingly clear that microglia, like macrophages, have at least two polarized activation states: Signal transducer and activators of transcription 6 (STAT6) is activated by IL-4 and IL-13 and plays an important role in alternative activation. PPARγ is a member of the nuclear hormone receptor superfamily and is considered to associate with lipid metabolism, oxidative metabolism, macrophage and microglia M2 polarization [12,13,14]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
