Ectopic Expression Of Cd74 In Ikk Beta-Deleted Mouse Hepatocytes

CD74, a Type II membrane glycoprotein and MHC class II chaperone involved in antigen processing, is normally expressed by cells associated with the immune system. CD74 also forms heterodimers with CD44 to generate receptors to macrophage migration inhibitory factor (MIF), a proinflammatory cytokine. Following targeted Alb-Cre-mediated deletion of Ikk beta in Ikk beta(Delta hep) mice (Ikk beta(F/F):Alb-Cre, a strain highly susceptible to chemically induced hepatotoxicity and hepatocarcinogenesis), CD74 is expressed abundantly by adult hepatocytes throughout liver acini, albeit more intensely in midzonal-to-centrilobular regions. By comparison, CD74 expression is not observed in Ikk beta(F/F). hepatocytes, nor is it augmented in the livers of Ikk beta(+/+):Alb-Cre mice; CD74 is barely detectable in cultured embryonic fibroblasts from Ikk beta(-/-) mice. Microarray profiling shows that constitutive CD74 expression in Ikk beta(Delta hep) hepatocytes is accompanied by significantly augmented expression of CD44 and key genes associated with antigen processing and host defense, including MHC class II I-A alpha, I-A beta, and I-E beta chains, CIITA and CD86. Taken together, these observations suggest that Ikk beta(Delta hep) hepatocytes might express functional capacities for class II-restricted antigen presentation and heightened responsiveness to MIF-signaling, and also suggest further roles for intrahepatocellular IKK beta in the suppression or inactivation of molecules normally associated with the formation and differentiation of cells of the immune system. (C) 2010 Elsevier GmbH. All rights reserved.