Resolvin D1 promotes the interleukin-4-induced alternative activation in BV-2 microglial cells.
BACKGROUND
Microglia 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.


METHODS
BV-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).


RESULTS
RvD1 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).


CONCLUSIONS
Our 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.
Longyan
L
Li
Yan
Y
Wu
Yanping
Y
Wang
Jing
J
Wu
Limin
L
Song
Wenjing
W
Xian
Shiying
S
Yuan
Lei
L
Pei
Department of Critical Care Medicine, Institute of Anesthesia and Critical Care, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. you_shang@yahoo.com.
You
Y
Shang
D000704:Analysis of Variance; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001119:Arginase / Q000378:metabolism; D002461:Cell Line, Transformed; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism; D024202:Electrophoretic Mobility Shift Assay; D015847:Interleukin-4 / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology; D000077339:Leflunomide; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D047495:PPAR gamma / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D050800:STAT6 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D000893:Anti-Inflammatory Agents; D007555:Isoxazoles; D047495:PPAR gamma; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C518399:resolvin D1; C079109:N-(3-pyridylmethyl)adriamycin; D015847:Interleukin-4; D004281:Docosahexaenoic Acids; D004317:Doxorubicin; C544448:Arg1 protein, mouse; D001119:Arginase; D000077339:Leflunomide