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http://hdl.handle.net/2445/201835
Title: | Distinct Responses to IL4 in Macrophages Mediated by JNK |
Author: | Arpa Toribio, Luis Batlle, Carlos Jiang, Peijin Caelles Franch, Carme Lloberas Cavero, Jorge Celada Cotarelo, Antonio |
Keywords: | Macròfags Inflamació Macrophages Inflammation |
Issue Date: | 11-Apr-2023 |
Publisher: | MDPI |
Abstract: | IL(Interleukin)-4 is the main macrophage M2-type activator and induces an anti-inflammatory phenotype called alternative activation. The IL-4 signaling pathway involves the activation of STAT (Signal Transducer and Activator of Transcription)-6 and members of the MAPK (Mitogen-activated protein kinase) family. In primary-bone-marrow-derived macrophages, we observed a strong activation of JNK (Jun N-terminal kinase)-1 at early time points of IL-4 stimulation. Using selective inhibitors and a knockout model, we explored the contribution of JNK-1 activation to macrophages' response to IL-4. Our findings indicate that JNK-1 regulates the IL-4-mediated expression of genes typically involved in alternative activation, such as Arginase 1 or Mannose receptor, but not others, such as SOCS (suppressor of cytokine signaling) 1 or p21Waf−1 (cyclin dependent kinase inhibitor 1A). Interestingly, we have observed that after macrophages are stimulated with IL-4, JNK-1 has the capacity to phosphorylate STAT-6 on serine but not on tyrosine. Chromatin immunoprecipitation assays revealed that functional JNK-1 is required for the recruitment of co-activators such as CBP (CREB-binding protein)/p300 on the promoter of Arginase 1 but not on p21Waf−1. Taken together, these data demonstrate the critical role of STAT-6 serine phosphorylation by JNK-1 in distinct macrophage responses to IL-4. |
Note: | Reproducció del document publicat a: https://doi.org/10.3390/cells12081127 |
It is part of: | Cells, 2023, vol. 12, num. 8, p. 1127-1144 |
URI: | http://hdl.handle.net/2445/201835 |
Related resource: | https://doi.org/10.3390/cells12081127 |
ISSN: | 2073-4409 |
Appears in Collections: | Articles publicats en revistes (Biologia Cel·lular, Fisiologia i Immunologia) Articles publicats en revistes (Bioquímica i Fisiologia) |
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