title: Thioredoxin-interacting protein gene expression via MondoA is rapidly and transiently suppressed during inflammatory responses.
abstract: Whereas accumulating evidence indicates that a number of inflammatory genes are induced by activation of nuclear factor-κB and other transcription factors, less is known about genes that are suppressed by proinflammatory stimuli. Here we show that expression of thioredoxin-interacting protein (Txnip) is dramatically suppressed both in mRNA and protein levels upon stimulation with lipopolysaccharide in mouse and human macrophages. In addition to lipopolysaccharide, a Toll-like receptor 4 ligand, stimulation with other Toll-like receptor ligands such as CpG DNA also suppressed Txnip expression. Not only the Toll-like receptor ligands, but also other proinflammatory stimulators, such as interleukin-1β and tumor necrosis factor-α elicited the similar response in fibroblasts. Suppression of Txnip by lipopolysaccharide is accompanied by a decrease of the glucose sensing transcription factor MondoA in the nuclei and dissociation of the MondoA:Mlx complex that bound to the carbohydrate-response elements in the Txnip promoter in unstimulated cells. Lipopolysaccharide-mediated decrease of nuclear MondoA was inhibited in the presence of 2-deoxyglucose. Furthermore, blockage of glyceraldehyde-3-phosphate dehydrogenase by iodoacetate alleviated the suppression of Txnip mRNA by lipopolysaccharide, suggesting the involvement of glucose-metabolites in the regulation. Since Txnip is implicated in the regulation of glucose metabolism, this observation links between inflammatory responses and metabolic regulation.
authors.affiliation: Laboratory of Cell Recognition and Response, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Kanari
authors.forename: Yuki
authors.initials: Y
authors.lastname: Sato
authors.forename: Satoru
authors.initials: S
authors.lastname: Aoyama
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Muta
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013879:Thioredoxins / Q000096:biosynthesis* / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D002352:Carrier Proteins; C508585:IL1B protein, human; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; C403128:MLX protein, human; C485496:MLXIP protein, human; C550079:MondoA protein, mouse; D012333:RNA, Messenger; C495345:TLR4 protein, human; C486715:TXNIP protein, human; C501970:Tcfl4 protein, mouse; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C445672:Txnip protein, mouse; C440499:lipopolysaccharide, Escherichia coli O111 B4; D013879:Thioredoxins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D005947:Glucose