| First Author | Hanihara F | Year | 2013 |
| Journal | Int Immunol | Volume | 25 |
| Issue | 9 | Pages | 531-44 |
| PubMed ID | 23728777 | Mgi Jnum | J:200520 |
| Mgi Id | MGI:5508814 | Doi | 10.1093/intimm/dxt017 |
| Citation | Hanihara F, et al. (2013) Transcriptional and post-transcriptional regulation of IkappaB-zeta upon engagement of the BCR, TLRs and FcgammaR. Int Immunol 25(9):531-44 |
| abstractText | IkappaB-zeta is a nuclear IkappaB protein robustly induced in macrophages and fibroblasts upon TLR or IL-1R stimulation. IkappaB-zeta associates with NF-kappaB in the cell nucleus and is essential for the induction of a subset of secondary response genes represented by IL-6. Here, we analyzed induction of IkappaB-zeta in mouse B cells and found that IkappaB-zeta is induced by BCR or TLR stimulation. Similar to TLR stimulation, BCR stimulation elicited NF-kappaB-mediated transcriptional activation and mRNA stabilization of IkappaB-zeta via a cis-element in IkappaB-zeta mRNA. Proteasome inhibitors inhibited transcriptional activation but not post-transcriptional activation, indicating independency of the two signals. Co-stimulation of the BCR and TLR9 or TLR7, but not TLR2/1, synergistically induced IkappaB-zeta. Co-engagement of inhibitory Fcgamma receptor suppressed BCR-mediated IkappaB-zeta expression but not that induced by TLR stimulation alone or co-stimulation of TLR and the BCR. The PI3K inhibitor LY294002 inhibited BCR-mediated, but not TLR-mediated, induction of IkappaB-zeta, consistent with the role of PI3K in BCR signaling and its suppression by FcgammaR. Analysis of IkappaB-zeta-deficient B cells demonstrated that IkappaB-zeta was essential upon stimulation of BCR or TLR for the expression of several genes including IL-10 and CTLA4. IkappaB-zeta-deficient B cells exhibited impaired proliferation and enhanced up-regulation of CD86 following stimulation of TLR9, but not the BCR, indicating critical roles for IkappaB-zeta in TLR signaling in B cells. Strict regulatory mechanisms for the induction of IkappaB-zeta via multiple pathways and its essential function upon stimulation indicate that IkappaB-zeta plays an important role in B cells. |
