| First Author | Bhattacharyya S | Year | 2004 |
| Journal | Blood | Volume | 104 |
| Issue | 4 | Pages | 1100-9 |
| PubMed ID | 15113757 | Mgi Jnum | J:92641 |
| Mgi Id | MGI:3054158 | Doi | 10.1182/blood-2003-12-4302 |
| Citation | Bhattacharyya S, et al. (2004) Immunoregulation of dendritic cells by IL-10 is mediated through suppression of the PI3K/Akt pathway and of I{kappa}B kinase activity. Blood 104(4):1100-1109 |
| abstractText | Interleukin-10 (IL-10) has potent immunoregulatory effects on the maturation and the antigen-presenting cell (APC) function of dendritic cells (DCs). The molecular basis underlying these effects in DCs, however, is ill defined. It is well established that the transcription factor NF-kappaB is a key regulator of DC development, maturation, and APC function. This study was initiated to determine the effects of IL-10 on the NF-kappaB signaling pathway in immature DCs. IL-10 pretreatment of myeloid DCs cultured from bone marrow resulted in reduced DNA binding and nuclear translocation of NF-kappaB after anti-CD40 antibody or lipopolysaccharide (LPS) stimulation. Furthermore, inhibited NF-kappaB activation was characterized by reduced degradation, phosphorylation, or both of IkappaBalpha and IkappaBepsilon but not IkappaBbeta and by reduced phosphorylation of Ser536, located in the trans-activation domain of p65. Notably, IL-10-mediated inhibition of NF-kappaB coincided with suppressed IkappaB kinase (IKK) activity in vitro. Furthermore, IL-10 blocked inducible Akt phosphorylation, and inhibitors of phosphatidylinositol 3-kinase (PI3K) effectively suppressed the activation of Akt, IKK, and NF-kappaB. These findings demonstrate that IL-10 targets IKK activation in immature DCs and that suppressing the PI3K pathway in part mediates blockade of the pathway. |
