Immature dendritic cells (iDCs) can be instructed to polarize the immune response toward a noninflammatory pathway by mediators that increase the intracellular concentration of cAMP. This phenomenon is associated with the ability of the cyclic nucleoside to inhibit the release of pro-inflammatory cytokines without affecting the differentiation process of the dendritic cells (DCs). Here we investigated the ability of cAMP to modulate the endotoxin signaling by exposing DCs to exogenous 8-bromium-cyclic AMP in the presence or absence of H89, a selective inhibitor of the protein kinase A, one of the major molecular targets of the cyclic nucleoside. cAMP affects the early lipopolysaccharide-induced signaling cascade dissociating the activation of NF-kappa B, p38, and ERK pathways from the stimulation of c-Src and Lyn kinases. This phenomenon was prevented by H89. The pharmacological block of Src-like tyrosine kinases induces comparable results confirming the involvement of this family of enzymes in the mechanism controlling the release of cytokines in human monocyte-derived iDCs. We propose that the cAMP-protein kinase A-dependent pathway regulates the functional plasticity of iDCs by gating the Toll-like receptor signaling at the level of Src-like kinases.

Cyclic AMP modulates the functional plasticity of immature dendritic cells by inhibiting Src-like kinases through protein kinase A-mediated signaling / Galgani, M.; De Rosa, V.; De Simone, S.; Leonardi, A.; D'Oro, U.; Napolitani, G.; Masci, A. M.; Zappacosta, S.; Racioppi, L.. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 279:31(2004), pp. 32507-32514. [10.1074/jbc.M403355200]

Cyclic AMP modulates the functional plasticity of immature dendritic cells by inhibiting Src-like kinases through protein kinase A-mediated signaling

Galgani M.;Masci A. M.;Zappacosta S.;Racioppi L.
2004

Abstract

Immature dendritic cells (iDCs) can be instructed to polarize the immune response toward a noninflammatory pathway by mediators that increase the intracellular concentration of cAMP. This phenomenon is associated with the ability of the cyclic nucleoside to inhibit the release of pro-inflammatory cytokines without affecting the differentiation process of the dendritic cells (DCs). Here we investigated the ability of cAMP to modulate the endotoxin signaling by exposing DCs to exogenous 8-bromium-cyclic AMP in the presence or absence of H89, a selective inhibitor of the protein kinase A, one of the major molecular targets of the cyclic nucleoside. cAMP affects the early lipopolysaccharide-induced signaling cascade dissociating the activation of NF-kappa B, p38, and ERK pathways from the stimulation of c-Src and Lyn kinases. This phenomenon was prevented by H89. The pharmacological block of Src-like tyrosine kinases induces comparable results confirming the involvement of this family of enzymes in the mechanism controlling the release of cytokines in human monocyte-derived iDCs. We propose that the cAMP-protein kinase A-dependent pathway regulates the functional plasticity of iDCs by gating the Toll-like receptor signaling at the level of Src-like kinases.
2004
Cyclic AMP modulates the functional plasticity of immature dendritic cells by inhibiting Src-like kinases through protein kinase A-mediated signaling / Galgani, M.; De Rosa, V.; De Simone, S.; Leonardi, A.; D'Oro, U.; Napolitani, G.; Masci, A. M.; Zappacosta, S.; Racioppi, L.. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 279:31(2004), pp. 32507-32514. [10.1074/jbc.M403355200]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/900502
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