Rabbit Anti-IRF2 monoclonal antibody, clone KK199-1

Retinal pigment epithelial (RPE) cells constitute the external part of the blood-retinal-barrier and play a pivotal role in the regulation of retinal immunity. In the present work, we investigated the effects of 15-deoxy-12,14-prostaglandin J2 (15 PGJ2), an endogenous ligand of PPAR gamma, on the IFN gamma-induced expression of MHC class II on RPE cells. Indeed, pathological expression of MHC class II molecules at the surface of RPE cells is a common feature of many blinding conditions. We demonstrated that 15 PGJ2 inhibited the IFN gamma-mediated induction of MHC class II on RPE cells without affecting the level of MHC class I and CD54 expression. The other PPAR gamma agonist rosiglitazone or troglitazone had no similar effects. Moreover, the inhibitory effect of 15 PGJ2 was not abrogated by co-incubation with PPAR gamma antagonists and did not involve the modulation of STAT-1, AKT or ERK1/2 phosphorylation, nor CIITA, IRF1 or IRF2 transcription. In conclusion, 15 PGJ2 inhibits strongly and specifically the IFN gamma-induced MHC class II expression on RPE cells by a PPAR gamma independent mechanism. Given the differential role of MHC classes I and II in the development of autoimmune uveitis and the potential toxicity of 15 PGJ2, our data's suggest that the development of novel small molecules targeting similar PPAR gamma independent pathways would be useful for the future management of uveitis. (c) 2006 Elsevier Inc. All rights reserved.

beta(2)-Microglobulin (beta(2)m) is a chaperone of major histocompatibility complex (MHC) class I (-like) molecules that play a central role in antigen presentation, immunoglobulin transport, and iron metabolism. It is therefore of importance that beta(2)m is adequately expressed in cells that perform these functions, such as hematopoietic cells. In this study, we investigated the transcriptional regulation Of beta(2)m in lymphoid and myeloid cell lines through a promoter containing a putative E box, Ets/interferon-stimulated response element (ISRE), and kappaB site. Here we show that upstream stimulatory factor 1 (USF1) and USF2 bind to the E box and regulate beta(2)m transactivation. The nuclear factor kappaB (NF-kappaB) sub-units p50 and p65 bind to the kappaB box and p65 transactivates beta(2)m. Interferon regulatory factor 1 (IRFI), IRF2, IRF4, and IRF8, but not PU.1, bind to the Ets/ISRE, and IRF1 and IRF3 are strong transactivators Of beta(2)m. Together, all 3 boxes are important for the constitutive and cytokine-induced levels Of beta(2)m expression in lymphoid and myeloid cell types. As such, beta(2)m transactivation is under the control of important transcriptional pathways, which are activated during injury, infection, and inflammation. (C) 2003 by The American Society of Hematology.