Functional consequences of CD36 downregulation by TLR signals
Por:
Zamora, C, Canto, E, Nieto, JC, Ortiz, MA, Juarez, C, Vidal, S
Publicada:
1 oct 2012
Resumen:
TLR recognition activates the secretion of pro- and anti-inflammatory cytokines and it also modulates the expression of crucial molecules involved in phagocytosis and antimicrobial activity. Scavenger receptors can act as TLR co-receptors or facilitate antigen loading. However, it remains unknown whether TLR can modulate the expression of these scavenger receptors. We stimulated human peripheral blood mononuclear cells (PBMC) with TLR2 (Pam3CSK4 and FSL1) and TLR4 ligand lipopolysaccharide (LPS) and then analyzed CD36 expression on different monocyte subpopulations by flow cytometry. TLR2 and TLR4 ligands can downregulate CD36 on the surface of monocytes, guiding the protein to intracellular compartments. Even though TLR-activation induced TNF alpha, IL-10 and IL-6 production, only recombinant TNF alpha was able to downregulate CD36. Neutralizing anti-TNF alpha antibodies showed that the Pam3CSK4 and FSL1-induced downregulation was partially mediated by TNFa but not by IL-6 or IL-10. However, LPS-induced downregulation could have also been caused by direct TLR4 targeting and signaling, and/or mediated by other unknown factors. CD36 downregulation reduced the capability of monocytes to phagocyte apoptotic neutrophils. In conclusion, modulation of scavenger receptor expression by TLR targeting on monocytes has functional consequences. Characterization this complex regulation may help us to understand this innate response and develop specific therapeutic drugs for each mechanism. (C) 2012 Elsevier Ltd. All rights reserved.
Filiaciones:
Zamora, C:
Hosp S Pau, Inst Recerca, Dep Immunol, Barcelona, Spain
Canto, E:
Hosp S Pau, Inst Recerca, Dep Immunol, Barcelona, Spain
Nieto, JC:
Hosp S Pau, Inst Recerca, Dep Immunol, Barcelona, Spain
Ortiz, MA:
Hosp S Pau, Inst Recerca, Dep Immunol, Barcelona, Spain
Vidal, S:
Hosp S Pau, Inst Recerca, Dep Immunol, Barcelona, Spain
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