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Calmodulin-dependent kinase IV links Toll-like receptor 4 signaling with survival pathway of activated dendritic cells

Authors :
Illario, M
Giardino Torchia, Ml
Sankar, U
Ribar, Tj
Galgani, M
Vitiello, L
Masci, Am
Bertani, Fr
Ciaglia, E
Astone, D
Maulucci, Giuseppe
Cavallo, A
Vitale, M
Cimini, V
Pastore, L
Means, Ar
Rossi, G
Racioppi, L.
Maulucci, Giuseppe (ORCID:0000-0002-2154-319X)
Illario, M
Giardino Torchia, Ml
Sankar, U
Ribar, Tj
Galgani, M
Vitiello, L
Masci, Am
Bertani, Fr
Ciaglia, E
Astone, D
Maulucci, Giuseppe
Cavallo, A
Vitale, M
Cimini, V
Pastore, L
Means, Ar
Rossi, G
Racioppi, L.
Maulucci, Giuseppe (ORCID:0000-0002-2154-319X)
Publication Year :
2008

Abstract

Microbial products, including lipopolysaccharide (LPS), an agonist of Toll-like receptor 4 (TLR4), regulate the lifespan of dendritic cells (DCs) by largely undefined mechanisms. Here, we identify a role for calcium-calmodulin–dependent kinase IV (CaMKIV) in this survival program. The pharmacologic inhibition of CaMKs as well as ectopic expression of kinase-inactive CaMKIV decrease the viability of monocyte-derived DCs exposed to bacterial LPS. The defect in TLR4 signaling includes a failure to accumulate the phosphorylated form of the cAMP response element-binding protein (pCREB), Bcl-2, and Bcl-xL. CaMKIV null mice have a decreased number of DCs in lymphoid tissues and fail to accumulate mature DCs in spleen on in vivo exposure to LPS. Although isolated Camk4−/− DCs are able to acquire the phenotype typical of mature cells and release normal amounts of cytokines in response to LPS, they fail to accumulate pCREB, Bcl-2, and Bcl-xL and therefore do not survive. The transgenic expression of Bcl-2 in CaMKIV null mice results in full recovery of DC survival in response to LPS. These results reveal a novel link between TLR4 and a calcium-dependent signaling cascade comprising CaMKIV-CREB-Bcl-2 that is essential for DC survival.

Details

Database :
OAIster
Notes :
English
Publication Type :
Electronic Resource
Accession number :
edsoai.on1105002944
Document Type :
Electronic Resource