RIP links TLR4 to Akt and is essential for cell survival in response to LPS stimulation

Marina S. Vivarelli, Douglas McDonald, Mendy Miller, Nicole Cusson, Michelle Kelliher, Raif S. Geha

Research output: Contribution to journalArticlepeer-review

Abstract

Receptor-interacting protein (RIP) has been reported to associate with tumor necrosis-associated factor (TRAF)2 and TRAF6. Since TRAF2 and TRAF6 play important roles in CD40 signaling and TRAF6 plays an important role in TLR4 signaling, we examined the role of RIP in signaling via CD40 and TLR4. Splenocytes from RIP-/- mice proliferated and underwent isotype switching normally in response to anti-CD40-IL-4 but completely failed to do so in response to LPS-IL-4. However, they normally up-regulated TNF-α and IL-6 gene expression and CD54 and CD86 surface expression after LPS stimulation. RIP-/- splenocytes exhibited increased apoptosis and impaired Akt phosphorylation after LPS stimulation. These results suggest that RIP is essential for cell survival after TLR4 signaling and links TLR4 to the phosphatidylinositol 3 kinase-Akt pathway.

Original languageEnglish
Pages (from-to)399-404
Number of pages6
JournalJournal of Experimental Medicine
Volume200
Issue number3
DOIs
Publication statusPublished - Aug 2 2004

Keywords

  • IκB
  • IL-6
  • NFκB
  • p38 MAP kinase
  • TNF-α

ASJC Scopus subject areas

  • Immunology

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