Rectal Administration of Lipopolysaccharide and Ovalbumin Ameliorates Acute Murine Colitis

Abstract

Repeated challenges of lipopolysaccharide (LPS) could reduce the expression of proinflammatory cytokines in vitro, and oral administration of ovalbumin (OVA) induces mucosal tolerance in vivo. However, the effect of local administration of LPS and OVA on experimental colitis in vivo remains unknown. This study was performed to elucidate the effect of rectal administration of LPS and OVA on an acute murine colitis induced by dextran sulfate sodium (DSS). BALB/c mice were rectally administered LPS with or without OVA followed by 3% DSS. Colitis was assessed by disease activity index (DAI) including weight loss, stool consistency and rectal bleeding, and histopathology. Primary colon epithelial cells were isolated and the expression of Toll-like receptor 4 (TLR4) was examined using the Western blot analysis. IL-6, IFN-γ and IL-10 mRNA levels in colonic tissue were assessed using real-time RT-PCR. LPS administration significantly attenuated the severity of acute DSS-induced colitis as assessed by DAI and histopathologic scoring compared with the control group. Combined treatment of LPS and OVA restored body weight loss and further ameliorated the severity of acute DSS colitis. LPS pretreatment regardless of OVA administration decreased TLR4 expression. LPS and OVA pretreatment reduced IL-6 and IFN-γ mRNA expression and increased IL-10 mRNA expression compared with controls. Rectal administration of LPS attenuated acute murine colitis, possibly through TLR4 down-regulation, and combined treatment of OVA additionally ameliorated colonic inflammation associated with up-regulation of IL-10.