2024-03-28T21:41:20Zhttp://digital.csic.es/dspace-oai/requestoai:digital.csic.es:10261/1243842021-11-22T13:07:48Zcom_10261_22com_10261_1col_10261_275
DIGITAL.CSIC
author
Sanz, Carlos
author
Fernández, Margarita
author
Alemany, Susana
funder
National Institutes of Health (US)
funder
Ministerio de Economía y Competitividad (España)
2015-11-03T13:03:40Z
2015-11-03T13:03:40Z
2014
Journal of Leukocyte Biology 95(6): 917-930 (2014)
http://hdl.handle.net/10261/124384
10.1189/jlb.0913486
http://dx.doi.org/10.13039/100000002http://dx.doi.org/10.13039/501100003329
24532642
Whereas the main function of APN is to enhance insulin activity, it is also involved in modulating the macrophage phenotype. Here, we demonstrate that at physiological concentrations, APN activates Erk1/2 via the IKKβ-p105/NF-κΒ1-Cot/tpl2 intracellular signal transduction cassette in macrophages. In peritoneal macrophages stimulated with APN, Cot/tpl2 influences the ability to phagocytose beads. However, Cot/tpl2 did not modulate the known capacity of APN to decrease lipid content in peritoneal macrophages in response to treatment with oxLDL or acLDL. A microarray analysis of gene-expression profiles in BMDMs exposed to APN revealed that APN modulated the expression of ~3300 genes; the most significantly affected biological functions were the inflammatory and the infectious disease responses. qRT-PCR analysis of WT and Cot/tpl2 KO macrophages stimulated with APN for 0, 3, and 18 h revealed that Cot/tpl2 participated in the up-regulation of APN target inflammatory mediators included in the cytokine-cytokine receptor interaction pathway (KEGG ID 4060). In accordance with these data, macrophages stimulated with APN increased secretion of cytokines and chemokines, including IL-1β, IL-1α, TNF-α, IL-10, IL-12, IL-6, and CCL2. Moreover, Cot/tpl2 also played an important role in the production of these inflammatory mediators upon stimulation of macrophages with APN. It has been reported that different types of signals that stimulate TLRs, IL-1R, TNFR, FcγR, and proteinase-activated receptor-1 activate Cot/tpl2. Here, we demonstrate that APN is a new signal that activates the IKKβ-p105/NF-κΒ1-Cot/tpl2-MKK1/2-Erk1/2 axis in macrophages. Furthermore, this signaling cassette modulates the biological functions triggered by APN in macrophages.
eng
closedAccess
Cot/tpl2 participates in the activation of macrophages by adiponectin
artículo
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https://digital.csic.es/bitstream/10261/124384/1/accesoRestringido.pdf
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accesoRestringido.pdf.txt
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accesoRestringido.pdf.txt