Bushell, Kristen N.Leeman, Susan E.Gillespie, EarlGower, Adam C.Reed, Karen L.Stucchi, Arthur F.Becker, James M.Amar, Salomon2020-05-072020-05-072011Kristen N. Bushell, Susan E. Leeman, Earl Gillespie, Adam C. Gower, Karen L. Reed, Arthur F. Stucchi, James M. Becker, Salomon Amar. 2011. "LITAF mediation of increased TNF-α secretion from inflamed colonic lamina propria macrophages.." PLoS One, Volume 6, Issue 9, https://doi.org/10.1371/journal.pone.00258491932-6203https://hdl.handle.net/2144/40661Dysregulation 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.en-UShttp://creativecommons.org/licenses/by/4.0/AnimalsBlotting, westernColonDNA-binding proteinsEnzyme-linked immunosorbent assayInflammationLipopolysaccharidesMacrophagesMiceMice, inbred C57BLMucous membraneNuclear proteinsPeroxidaseReverse transcriptase polymerase chain reactionTranscription factorsTumor necrosis factor-alphaGeneral science & technologyArticle10.1371/journal.pone.0025849109662