title: LITAF mediation of increased TNF-α secretion from inflamed colonic lamina propria macrophages.
abstract: Dysregulation of TNF-α in lamina propria macrophages (LPM) is a feature of inflammatory bowel diseases (IBD). LPS-Induced-TNF-Alpha-Factor (LITAF) is a transcription factor that mediates TNF-α expression. To determine whether LITAF participates in the mediation of TNF-α expression in acutely inflamed colonic tissues, we first established the TNBS-induced colonic inflammation model in C57BL/6 mice. LPM were harvested from non-inflamed and inflamed colonic tissue and inflammatory parameters TNF-α and LITAF mRNA and protein levels were measured ex-vivo. LPM from TNBS-treated mice secreted significantly more TNF-α at basal state and in response to LPS than LPM from untreated mice (p<0.05). LITAF mRNA and protein levels were elevated in LPM from TNBS compared with untreated animals and LPS further increased LITAF protein levels in LPM from inflamed tissue (P<0.05). To further confirm the role of LITAF in acutely inflamed colonic tissues, TNBS-induced colonic inflammation was produced in LITAF macrophage specific knockout mice (LITAF mac -/- mice) and compared to wild type (WT) C57BL/6. Twenty four hours following TNBS administration, colonic tissue from LITAF mac -/- mice had less MPO activity and reduced colonic TNF-α mRNA then WT C57BL/6 mice (p<0.05). LPM harvested from LITAF mac -/- secreted significantly less TNF-α in response to LPS than wild type (WT) C57BL/6 (p<0.05). This study provides evidence that LITAF contributes to the regulation of TNF-α in LPM harvested following acute inflammation or LPS treatment paving the way for future work focusing on LITAF inhibitors in the treatment of TNF-α-mediated inflammatory conditions.
authors: Boston University School of Medicine Department of Pharmacology and Experimental Therapeutics, Boston, Massachusetts, United States of America.
authors: Kristen N
authors: KN
authors: Bushell
authors: Susan E
authors: SE
authors: Leeman
authors: Earl
authors: E
authors: Gillespie
authors: Adam C
authors: AC
authors: Gower
authors: Karen L
authors: KL
authors: Reed
authors: Arthur F
authors: AF
authors: Stucchi
authors: James M
authors: JM
authors: Becker
authors: Salomon
authors: S
authors: Amar
mesh_terms: D000818:Animals; D015153:Blotting, Western; D003106:Colon / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D004268:DNA-Binding Proteins; D004797:Enzyme-Linked Immunosorbent Assay; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000166:cytology*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D009195:Peroxidase / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; C492727:Litaf protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase