Decrease in cAMP levels modulates adhesion to fibronectin and immunostimulatory ability of human dendritic cells.
The aim of the present study was to analyze the early events elicited by tumor necrosis factor alpha (TNF-alpha) on monocyte-derived dendritic cells (moDC) adhesion to fibronectin (FN) and the involvement of cAMP in the signal transduction mechanism. The intracellular concentration of cAMP and moDC adhesion to FN decreased after TNF-alpha treatment. An inverted dose-dependency for TNF-alpha effect was observed for adhesion and cAMP levels. The presence of a phosphodiesterase (PDE) inhibitor (IBMX) and cAMP analogs (8Br-cAMP, Db-cAMP) reversed the observed TNF-alpha effects. The role of cAMP was analyzed further by examining the cAMP levels in nonadhered and adhered, TNF-alpha-treated moDC. Nonadhered moDC showed lower cAMP levels compared with adhered moDC. Furthermore, nonadhered moDC showed higher IL-12 content and allostimulatory ability compared with adhered moDC. The higher allostimulatory capacity was abolished in the presence of cAMP analogs and a PDE inhibitor. These results suggest that cAMP levels correlate with TNF-alpha-induced changes of moDC adhesion and allostimulatory capacity.
Burzyn
Dalia
D
Laboratorio de Inmunogenética, Hospital de Clínicas "José de San Martín", Facultad de Medicina, Universidad de Buenos Aires, Avenida Córdoba 2351 (C.P. 1120), Buenos Aires, Argentina.
Jancic
Carolina C
CC
Zittermann
Sandra
S
Keller Sarmiento
María I
MI
Fainboim
Leonardo
L
Rosenstein
Ruth E
RE
Chuluyan
H Eduardo
HE
D002448:Cell Adhesion; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D005353:Fibronectins / Q000378:metabolism*; D006801:Humans; D018664:Interleukin-12 / Q000096:biosynthesis; D008213:Lymphocyte Activation; D009000:Monocytes / Q000276:immunology; D013234:Stem Cells / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D005353:Fibronectins; D014409:Tumor Necrosis Factor-alpha; D018664:Interleukin-12; D000242:Cyclic AMP