Artículos de revistas
Phosphatidylinositol 3-kinase interacts with the glucocorticoid receptor upon TLR2 activation
Fecha
2011Registro en:
Journal of Cellular and Molecular Medicine, Volumen 15, Issue 2, 2018, Pages 339-349
15821838
10.1111/j.1582-4934.2009.00958.x
Autor
Arancibia, Sergio
Benítez, Dixán
Núñez, Lucia E.
Jewell, Christine M.
Langjahr, Patricia
Candia, Enzo
Zapata Torres, Gerald
Cidlowski, John A.
González Burgos, María Julieta
Hermoso Ramello, Marcela
Institución
Resumen
Airway inflammation is a common condition where glucocorticoids (GC) are a well-established therapy. It has been demonstrated that GC stimulate components of innate immunity. Specifically, GC up-regulate TLR2 expression and activation upon inflammatory stimuli; however, little is known about the signalling involved in this process. To determine the mechanism by which dexamethasone modulates TLR2-induced cytokine production this signalling pathway was monitored in a lung epithelial cell line exposed to the TLR2 synthetic agonist, Pam 3-Cys-Ser-Lys 4. These experiments demonstrate that phosphatidylinositol 3-kinase (PI3K) is critical for the TLR2 downstream effects of GC. Cells expressing a PI3K mutant (p85-dominant negative, DN; p85 Δ478-511) and exposed to Pam 3-Cys-Ser-Lys 4 in the presence or absence of dexamethasone, showed enhanced tumour necrosis factor (TNF)α expression while AP-1 and NF-κB transcriptional activity were repressed. We provide experimental evidence that PI3K physic