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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Galgani, M; De Rosa, V; De Simone, S; Leonardi, A; D'Oro, U; Napolitani, G; Masci, AM; Zappacosta, S; Racioppi, L

Published Date

  • July 1, 2004

Published In

Volume / Issue

  • 279 / 31

Start / End Page

  • 32507 - 32514

PubMed ID

  • 15166249

Pubmed Central ID

  • 15166249

Electronic International Standard Serial Number (EISSN)

  • 1083-351X

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.m403355200

Language

  • eng