LITAF Mediation of Increased TNF-alpha Secretion from Inflamed Colonic Lamina Propria Macrophages

作者：Bushell Kristen N^*; Leeman Susan E; Gillespie Earl; Gower Adam C; Reed Karen L; Stucchi Arthur F; Becker James M; Amar Salomon

来源：PLos One, 2011, 6(9): e25849.

DOI：10.1371/journal.pone.0025849

Dysregulation of TNF-alpha 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-alpha expression. To determine whether LITAF participates in the mediation of TNF-alpha 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-alpha and LITAF mRNA and protein levels were measured ex-vivo. LPM from TNBS-treated mice secreted significantly more TNF-alpha 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-alpha mRNA then WT C57BL/6 mice (p<0.05). LPM harvested from LITAF mac-/-secreted significantly less TNF-alpha 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-alpha in LPM harvested following acute inflammation or LPS treatment paving the way for future work focusing on LITAF inhibitors in the treatment of TNF-alpha-mediated inflammatory conditions.

• 出版日期2011-9-30