NOTCH3 signaling is essential for NF-κB activation in TLR-activated macrophages.

Autor: López-López S; Universidad de Castilla-La Mancha, Medical School/CRIB, Laboratory of Biochemistry and Molecular Biology, Department of Inorganic and Organic Chemistry and Biochemistry, UCLM, C/Almansa 14, 02008, Albacete, Spain.; Unidad Asociada de Biomedicina UCLM, Unidad Asociada CSIC, Albacete, Spain., Monsalve EM; Universidad de Castilla-La Mancha, Medical School/CRIB, Laboratory of Biochemistry and Molecular Biology, Department of Inorganic and Organic Chemistry and Biochemistry, UCLM, C/Almansa 14, 02008, Albacete, Spain.; Unidad Asociada de Biomedicina UCLM, Unidad Asociada CSIC, Albacete, Spain., Romero de Ávila MJ; Universidad de Castilla-La Mancha, Medical School/CRIB, Laboratory of Biochemistry and Molecular Biology, Department of Inorganic and Organic Chemistry and Biochemistry, UCLM, C/Almansa 14, 02008, Albacete, Spain.; Unidad Asociada de Biomedicina UCLM, Unidad Asociada CSIC, Albacete, Spain., González-Gómez J; Universidad de Castilla-La Mancha, CRIB/Biomedicine Unit, Pharmacy School, UCLM/CSIC, C/Almansa 14, 02008, Albacete, Spain., Hernández de León N; University Hospital Complex of Albacete, 02008, Albacete, Spain., Ruiz-Marcos F; University Hospital Complex of Albacete, 02008, Albacete, Spain., Baladrón V; Universidad de Castilla-La Mancha, Medical School/CRIB, Laboratory of Biochemistry and Molecular Biology, Department of Inorganic and Organic Chemistry and Biochemistry, UCLM, C/Almansa 14, 02008, Albacete, Spain.; Unidad Asociada de Biomedicina UCLM, Unidad Asociada CSIC, Albacete, Spain., Nueda ML; Universidad de Castilla-La Mancha, CRIB/Biomedicine Unit, Pharmacy School, UCLM/CSIC, C/Almansa 14, 02008, Albacete, Spain., García-León MJ; Department of Cell Biology and Immunology, Centro de Biología Molecular Severo Ochoa (CSIC), Universidad Autónoma de Madrid, 28049, Madrid, Spain.; INSERM UMR_S1109, Tumor Biomechanics, 67000, Strasbourg, France.; Université de Strasbourg, 67000, Strasbourg, France.; Fédération de Médecine Translationnelle de Strasbourg (FMTS), 67000, Strasbourg, France., Screpanti I; Department of Molecular Medicine, Sapienza University, Viale Regina Elena 291, 00161, Roma, Italy., Felli MP; Department of Experimental Medicine, Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy., Laborda J; Universidad de Castilla-La Mancha, CRIB/Biomedicine Unit, Pharmacy School, UCLM/CSIC, C/Almansa 14, 02008, Albacete, Spain., García-Ramírez JJ; Universidad de Castilla-La Mancha, Medical School/CRIB, Laboratory of Biochemistry and Molecular Biology, Department of Inorganic and Organic Chemistry and Biochemistry, UCLM, C/Almansa 14, 02008, Albacete, Spain. josejavier.gramirez@uclm.es.; Unidad Asociada de Biomedicina UCLM, Unidad Asociada CSIC, Albacete, Spain. josejavier.gramirez@uclm.es., Díaz-Guerra MJM; Universidad de Castilla-La Mancha, Medical School/CRIB, Laboratory of Biochemistry and Molecular Biology, Department of Inorganic and Organic Chemistry and Biochemistry, UCLM, C/Almansa 14, 02008, Albacete, Spain. mariajose.martinez@uclm.es.; Unidad Asociada de Biomedicina UCLM, Unidad Asociada CSIC, Albacete, Spain. mariajose.martinez@uclm.es.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2020 Sep 09; Vol. 10 (1), pp. 14839. Date of Electronic Publication: 2020 Sep 09.
DOI: 10.1038/s41598-020-71810-4
Abstrakt: Macrophage activation by Toll receptors is an essential event in the development of the response against pathogens. NOTCH signaling pathway is involved in the control of macrophage activation and the inflammatory processes. In this work, we have characterized NOTCH signaling in macrophages activated by Toll-like receptor (TLR) triggering and determined that DLL1 and DLL4 are the main ligands responsible for NOTCH signaling. We have identified ADAM10 as the main protease implicated in NOTCH processing and activation. We have also observed that furin, which processes NOTCH receptors, is induced by TLR signaling in a NOTCH-dependent manner. NOTCH3 is the only NOTCH receptor expressed in resting macrophages. Its expression increased rapidly in the first hours after TLR4 activation, followed by a gradual decrease, which was coincident with an elevation of the expression of the other NOTCH receptors. All NOTCH1, 2 and 3 contribute to the increased NOTCH signaling detected in activated macrophages. We also observed a crosstalk between NOTCH3 and NOTCH1 during macrophage activation. Finally, our results highlight the relevance of NOTCH3 in the activation of NF-κB, increasing p65 phosphorylation by p38 MAP kinase. Our data identify, for the first time, NOTCH3 as a relevant player in the control of inflammation.
Databáze: MEDLINE
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