Superfund Research Program
Detection and Models of Toxicant Exposure
Center Director: Robert H. Tukey
Grant Number: P42ES010337
Funding Period: 2000-2023
Program Links
Title: Comparisons between liver tissues and freshly isolated hepatocytes from Ikk F/F and Ikk Dhep (Ikk -deleted) mice
Accession Number: GSE15476
Link to Dataset: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE15476
Repository: Gene Expression Omnibus (GEO)
Data Type(s): Gene Expression
Experiment Type(s): Expression profiling by array
Organism(s): Mus musculus
Summary: 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 Ikk in Ikk DeltaHep 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 Ikk F/F hepatocytes or embryonic fibroblasts from Ikk -/- mice. Constitutive CD74 expression in Ikk DeltaHep hepatocytes is also accompanied by significantly augmented expression of CD44 and genes associated with antigen processing and host defense. These observations suggest that Ikk DeltaHep hepatocytes might directly respond to MIF signaling, accounting partly for the enhanced susceptibility of Ikk DeltaHep mice to hepatotoxins and hepatocarcinogens, and also might exhibit unusual immunological properties including antigen presentation.
Publication(s) associated with this dataset:- Uhlenhaut N, Barish GD, Yu RT, Downes M, Karunasiri M, Liddle C, Schwalie P, Hubner N, Evans RM. 2013. Insights into negative regulation by the glucocorticoid receptor from genome-wide profiling of inflammatory cistromes. Mol Cell 49(1):158-171. doi:10.1016/j.molcel.2012.10.013 PMID:23159735 PMCID:PMC3640846