An Autocrine Regulator Loop Involving Tumor Necrosis Factor and Chemokine (C-C motif) Ligand-2 Is Activated by Transforming Growth Factor-ß in Rat Basophilic Leukemia-2H3 Mast Cells
Por:
Avila-Rodríguez, D, Ibarra-Sánchez, A, Sosa-Garrocho, M, Vázquez-Victorio, G, Caligaris, C, Anaya-Rubio, I, Segura-Villalobos, D, Blank, U, González-Espinosa, C, Macias-Silva, M
Publicada:
30 abr 2025
Resumen:
TGF-beta is a pleiotropic cytokine with both stimulatory and inhibitory effects on immune cells, depending on the microenvironmental context. It targets mast cells (MCs) in different physio-pathological conditions, such as inflammation and cancer. Besides acting as a potent chemoattractant for MCs, TGF-beta regulates many other aspects of MCs' physiology, including the secretion of many regulatory molecules. MCs secrete a variety of mediators, either pre-formed or newly synthesized, upon appropriate stimulation. CCL-2 chemokine and TNF cytokine act as potent chemoattractants for several immune cells and participate in the initiation of inflammatory responses by recruiting them to injured tissues. TGF-beta regulates CCL-2 and TNF secretion in different cell types and under distinct cellular contexts. Here, we report that the treatment with TGF-beta alone induces the secretion of both pre-formed and newly synthesized CCL-2 in the rat RBL-2H3 mast cells but not in mouse bone marrow-derived mast cells (BMMCs). TGF-beta-induced CCL-2 secretion depends on rapid rearrangements of the actin cytoskeleton and, remarkably, on the early secretion of soluble TNF that triggers an autocrine TNF signaling. In conclusion, we found cooperation between TGF-beta and TNF signaling pathways to promote the secretion of CCL-2 chemokine by MCs in a cell-context specific manner.
Filiaciones:
Univ Nacl Autonoma Mexico, Inst Fisiol Celular, Ciudad Mexico 04510, Mexico
Cinvestav, Ctr Invest & Estudios Avanzados, Dept Farmacobiol, Ciudad Mexico 14400, Mexico
Ctr Invest Envejecimiento, Ciudad Mexico 14400, Mexico
Univ Nacl Autonoma Mexico, Fac Ciencias, Ciudad Mexico 04510, Mexico
Univ Paris Cite, Ctr Rech Inflammat, Lab Excellence Inflamex, INSERM,U1149,CNRS,EMR8252, F-75018 Paris, France
gold, All Open Access; Gold Open Access
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