Activation of src-family tyrosine kinases by LPS regulates cytokine production in dendritic cells by controlling AP-1 formation.

Published

Journal Article

The role of src-family tyrosine kinases in LPS-induced DC maturation has not been fully addressed. We show that LPS induces activation of c-Src and Lyn in human DC. Inhibition of these kinasesby PP1 uncoupled LPS-induced cytokine production from the up-regulation of costimulatory molecules, resulting in DC still capable of stimulating T cell proliferation but much less efficient in inducing Th1 differentiation. This is the first example of a pharmacological inhibitor able to modulate the capacity of DC to induce a particular type of immune response. Inhibition of src-family kinases impaired phosphorylation and accumulation of c-Jun, leading to reduced formation of AP-1 complexes upon LPS stimulation. Thus, src-kinases control cytokine production in LPS-induced DC maturation through a timely formation of AP-1.

Full Text

Duke Authors

Cited Authors

  • Napolitani, G; Bortoletto, N; Racioppi, L; Lanzavecchia, A; D'Oro, U

Published Date

  • October 1, 2003

Published In

Volume / Issue

  • 33 / 10

Start / End Page

  • 2832 - 2841

PubMed ID

  • 14515267

Pubmed Central ID

  • 14515267

International Standard Serial Number (ISSN)

  • 0014-2980

Digital Object Identifier (DOI)

  • 10.1002/eji.200324073

Language

  • eng

Conference Location

  • Germany