First Author | Hirata N | Year | 2009 |
Journal | Cell Immunol | Volume | 258 |
Issue | 1 | Pages | 9-17 |
PubMed ID | 19361784 | Mgi Jnum | J:149493 |
Mgi Id | MGI:3848599 | Doi | 10.1016/j.cellimm.2009.03.006 |
Citation | Hirata N, et al. (2009) Selective regulation of interleukin-10 production via Janus kinase pathway in murine conventional dendritic cells. Cell Immunol 258(1):9-17 |
abstractText | In this study, we examined the role of JAKs in regulation of inflammatory versus anti-inflammatory cytokine balance in murine conventional dendritic cells (DCs). Highly purified lipopolysaccharide (upLPS) combined with imiquimod (IQ) synergistically induced IL-10 production by DCs, while each ligand alone showed a slight effect on the IL-10 production. Marked phosphorylation of JAK2, STAT1 and STAT3 was detected in DCs following upLPS plus IQ stimulation. Blocking the JAK pathway by JAK inhibitor I (JAKi) resulted in significant inhibition of IL-10 production by the DCs. However, JAKi showed negligible effect on the DC production of IL-12, IL-6 and TNF-alpha. JAKi completely blocked the TLR-mediated STATs activation, and attenuated the activation of Akt, a downstream effector of PI3K, in DCs stimulated by upLPS plus IQ. LY294002, a specific inhibitor of PI3K, markedly inhibited the DC production of IL-10. Thus, JAK-PI3K axis appeared to be responsible for the IL-10 production by DCs. |