INVESTIGADORES
AMARAL Maria Marta
congresos y reuniones científicas
Título:
Acidosis triggers IL-12 production by human dendritic cells: analysis of the mechanisms involved
Autor/es:
MARTÍNEZ DIEGO; VERMEULEN, MÓNICA; SABATTE JUAN; CEBALLOS ANA; AMARAL MARÍA M; COSO OMAR; GEFFNER, JORGE
Lugar:
Córdoba
Reunión:
Congreso; VII Congreso Latinoamericano de Inmunología (ALAI); 2005
Institución organizadora:
ASOCIACIÓN LATINOAMERICANA DE INMUNOLOGÍA
Resumen:
We have previously showed that extracellular acidosis (pH 6.5) triggers the production of IL-12 by human dendritic cells (DC). Here, we examined the mechanisms involved. DC were obtained from peripheral blood monocytes cultured for 6 days in the presence of GM-CSF and IL-4. In a first set of experiments we analyzed the signaling pathways activated in DC after exposure at pH 6.5. We found that acidosis triggers the phosphorylation of Akt (the main downstream target of PI3K) and the activation of the MAPKs ERK and p38, at 1-5 min after treatment. No degradation of IkB was found supporting that NF-kB is not activated by acidosis. To analyze the role of the phosphoinositide 3-kinase/Akt, and MAPK-dependent pathways in the production of IL- 12, DC were treated with different inhibitors for 30 min at 37oC at pH 7.3, and then cultured for 48 hs at pH 7.3 or 6.5. After this period, the production of IL-12 was analyzed in culture supernatants by ELISA. We found that Inhibition of PI3K by wortmannin (50 nM) as well as the inhibition of p38 MAPK by SB202190 (25 mM) decreased the production of IL-12 triggered by acidosis (% inhibition = 53 ± 12 and 44 ± 7, respectively, mean ± SEM, n=6, p< 0.01). On the contrary, the inhibition of MEK, the upstream kinase responsible for ERK activation, by PD98059 (50 mM), did not mediate any inhibitory effect. Our results support that acidosis triggers the production of IL-12 by DC via PI3K/Akt and p38 MAPK-dependent pathways.