Comparisons between liver tissues and freshly isolated hepatocytes from IkkβF/F and IkkβDhep (Ikkβ-deleted) mice

CD74, a Type II membrane glycoprotein and MHC class II chaperone (Ii), 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 Cre-mediated deletion of Ikkβ in IkkβDeltaHep mice (a strain highly susceptible to chemically-induced hepatotoxicity and hepatocarcinogenesis), CD74 is abundantly expressed by hepatocytes throughout liver acini (as detected by specific Western blots and immunohistochemical stains); it is not observed in either control IkkβF/F hepatocytes or embryonic fibroblasts from Ikkβ-/- mice. Constitutive CD74 expression in IkkβDeltaHep hepatocytes is also accompanied by significantly augmented expression of CD44 and genes associated with antigen processing and host defense. These observations suggest that IkkβDeltaHep hepatocytes might directly respond to MIF signaling, accounting partly for the enhanced susceptibility of IkkβDeltaHep mice to hepatotoxins and hepatocarcinogens, and also might exhibit unusual immunological properties including antigen presentation. Total RNA samples were obtained from four 6-8 week-old male mice. The four RNA samples were processed as described in the PROTOCOLS section below.