Role of lipopolysaccharide and IL-4 in control of transcription of the class II A alpha gene
Department of Medicine, Division of Rheumatology
Medical Subject Headings
Animals; Antigens, CD8; B-Lymphocytes; Base Sequence; Binding, Competitive; Cycloheximide; DNA-Binding Proteins; *Genes, MHC Class II; Histocompatibility Antigens Class II; Interleukin-4; Lipopolysaccharides; Male; Mice; Molecular Sequence Data; RNA, Messenger; Receptors, Antigen, T-Cell; Transcription, Genetic
Cellular and Molecular Physiology | Immunology and Infectious Disease | Molecular Genetics
The class II (Ia) MHC molecules are cell surface proteins that regulate the activation of T cells. B lymphocyte expression of class II molecules has been shown to be influenced by a number of external stimuli. It has been previously demonstrated that treatment of these cells with IL-4 leads to an increase in class II gene transcription at 18 h as well as to an increase in steady state class II mRNA. It has also been previously demonstrated that LPS treatment of splenic B cells from athymic mice results in a decrease in steady state mRNA encoding the A alpha class II protein. This decrease persists for at least 18 h. Nuclear run-on transcription assays now demonstrate that although steady state mRNA levels for A alpha are decreased by LPS treatment of athymic mouse lymphocytes, LPS does not decrease A alpha gene transcription, but rather modestly activates transcription of this class II gene. LPS and IL-4 have been demonstrated to be synergistic stimuli for a number of genes. Costimulation of splenic lymphocytes from athymic mice with IL-4 plus LPS leads to activation of transcription, but the increase in transcription is no more than that seen with IL-4 stimulation alone. However, in costimulated lymphocytes, steady state A alpha-encoding mRNA levels are intermediate between the increased levels seen with IL-4 stimulation and the decreased levels seen with LPS stimulation. Therefore, LPS and IL-4 act nonsynergistically in class II gene transcription and the effects of LPS in decreasing steady state mRNA are most likely posttranscriptional. An IL-4-inducible and an LPS-inducible DNA-binding protein have been previously identified in splenic lymphocytes from athymic mice. Both nuclear binding proteins form complexes with the same DNA fragments from a control region of the A alpha gene. These nucleoprotein complexes comigrate under nondenaturing conditions and display identical patterns of binding with a panel of oligonucleotide competitors. Oligonucleotides representing protein binding sites of the IL-4 and LPS-induced DNA-binding proteins cross-compete for protein binding. Therefore, the binding proteins induced by LPS and IL-4 are likely related, and may function at different efficiencies as activators of A alpha gene transcription.
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Citation: J Immunol. 1991 Oct 1;147(7):2377-83.
Gravallese, Ellen M.; Darling, Jama M.; Glimcher, Laurie H.; and Boothby, Mark, "Role of lipopolysaccharide and IL-4 in control of transcription of the class II A alpha gene" (1991). Rheumatology Publications and Presentations. 13.