PPAR-γ agonist pioglitazone regulates dendritic cells immunogenicity mediated by DC-SIGN via the MAPK and NF-κB pathways

- Pioglitazone activation of PPAR-γ reduces DC-SIGN expression in dendritic cells.
- Pioglitazone regulates dendritic cells immunogenicity mediated by DC-SIGN.
- Pioglitazone activation of PPAR-γ inhibits MAPK and NF-κB pathways in dendritic cells.
- DC-SIGN expression is regulated via the pathways of ERK, JNK and NF-κB, but not p38 MAPK.

Dendritic cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) is a dendritic cell-specific lectin which participates in dendritic cell (DC) trafficking, antigen uptake and DC-T cell interactions at the initiation of immune responses. This study investigated whether peroxisome proliferator-activated receptor-gamma (PPAR-γ) activation in human DCs regulates the immunogenicity of DCs mediated by DC-SIGN and exploited the possible molecular mechanisms, especially focused on the signaling pathways of mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB). Here, we show that the PPAR-γ agonist pioglitazone decreased DC adhesion and transmigration, and DC stimulation of T cell proliferation mediated by DC-SIGN dependent on activation of PPAR-γ, although it increased DC endocytosis independent of PPAR-γ activation. Furthermore, PPAR-γ activation by pioglitazone in DCs down-regulated the expression of DC-SIGN, which was mediated by modulating the balance of the signaling pathways of extracellular signal-regulated kinase, c-Jun N-terminal kinase and NF-κB, but not p38 MAPK. Therefore, we conclude that PPAR-γ activation in human DCs regulates the immunogenicity of DCs mediated by DC-SIGN via the pathways of MAPK and NF-κB. These findings may support the important role of these mediators in the regulation of DC-mediated inflammatory and immunologic processes.