Abstract
Dysregulation of TNF‐α secretion by lamina propria macrophages (LPM) is a hallmark of the inflammatory bowel disease Crohn's Disease (CD). LITAF has been shown to regulate TNF expression in macrophages and macrophage‐specific LITAF mac −/− mice (KO) are resistant to LPS induced sepsis. LITAF protein is increased by 30% in LPM isolated from C57BL/6 mice (WT) after TNBS administration, a well established model of CD (p<0.05). The aim of this study was to compare the colonic inflammatory responses of WT mice to LITAF mac−/− mice after administration of TNBS.Methods: WT and KO mice were administered TNBS (3 mg in 50% EtOH) rectally. After 24 hrs, body weights (BW) were determined and levels of the inflammatory marker myeloperoxidase (MPO) and TNF‐α mRNA were measured in colon tissue.Results: TNBS administration reduces BW in all animals compared to untreated controls (p<0.05); however, KO mice lost 50% less BW than the WT mice (p<0.05). MPO activity is five fold lower in KO mice compared to WT (p<0.05). Tissue levels of TNF‐α mRNA is also reduced in the KO compared to WT animals (376 ± 156 vs. 843± 253 copies) after TNBS administration.Conclusions:LITAF mac −/− have an attenuated inflammatory response to colonic TNBS administration. These results highlight a potential value of anti‐LITAF strategies for therapeutic management of CD. Research Support: BMC departments of Surgery and Pharmacology and NIDCR R01 DE014079.
Published Version
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