We had previously demonstrated that ectopic expression of interferon gamma (IFNgamma) in the lens induced lens pathology, inhibited the growth of the entire eye and altered the fate of cells destined to become lens fiber cells. These effects have been attributed in part to transcriptional activation of members of the interferon regulatory factor (IRF) family. In fiscal year 1997 we focused on analysis of the levels of these factors in the lens and in lens cell lines and on the transcriptional mechanisms underlying abnormal development in IFNgamma transgenic animals. Our results show that interferon consensus sequence binding protein (ICSBP), a member of the IRF family that is thought to be exclusively expressed in lymphoid cells, is constitutively expressed in the lens. ICSBP gene transcription is upregulated in the lens of IFNgamma transgenic mice with lens abnomalities and in lens cells treated with IFNgamma. DNA-protein binding studies with nuclear extracts of IFNgamma-treated lens cells further revealed activation of nuclear factors that bind specifically to the ICSBP GAS motif and the binding complex is supershifted by STAT1; similar interactions are not observed with IRF-1 GAS or IRF-2 and ISGF3gamma ISREs. It is of note that, ICSBP gene expression is absent in the NKR11 lens cell line derived from the Nakano mouse with early onset cataract, providing further suggestive evidence that the negative regulatory transcription factor ICSBP, may have novel, non-immunity related function(s) in lens epithelial cells and possibly other cell types.
| He, Chang; Yu, Cheng-Rong; Sun, Lin et al. (2015) Topical administration of a suppressor of cytokine signaling-1 (SOCS1) mimetic peptide inhibits ocular inflammation and mitigates ocular pathology during mouse uveitis. J Autoimmun 62:31-8 |
| Egwuagu, Charles E; Yu, Cheng-Hong; Mahdi, Rashid M et al. (2006) Cytokine-induced retinal degeneration: role of suppressors of cytokine signaling (SOCS) proteins in protection of the neuroretina. Adv Exp Med Biol 572:275-81 |
| Takase, H; Yu, C-R; Liu, X et al. (2005) Induction of suppressors of cytokine signaling (SOCS) in the retina during experimental autoimmune uveitis (EAU): potential neuroprotective role of SOCS proteins. J Neuroimmunol 168:118-27 |
| Egwuagu, Charles E; Yu, Cheng-Rong; Li, Zhuqing et al. (2005) SOCS5 mRNA levels in peripheral blood mononuclear cells (PBMC): a potential bio-marker for monitoring response of uveitis patients to Daclizumab therapy. J Autoimmun 24:39-46 |
