Oxazolone-induced colitis in BALB/C mice: a new method to evaluate the efficacy of therapeutic agents for ulcerative colitis.

A number of experimental models of colitis have been proposed. However, few studies have presented T helper-2 (Th-2) type colitis models that substitute for human ulcerative colitis (UC). In recent years, the murine oxazolone (OXA)-induced colitis model came to be accepted as a Th-2 type model, but it has yet to be used in any pharmacological study. In the present study, we modified the OXA-induced colitis model in BALB/C mice to evaluate the efficacy of treatments for UC. Colitis was induced by intrarectal administration of OXA solution (7.5 mg/mL in 40% ethanol) in a BALB/C strain that is known to favor Th-2 immune responses. A lower mortality rate was obtained in the BALB/C strain than was found in the original method. Histological examination showed that there were morphological similarities to human UC. Increased mRNA expression of interleukin-13, a Th-2 cytokine, was observed in mesenteric lymph nodes. Intrarectal administration of 5-aminosalicylic acid or sodium prednisolone phosphate resulted in a significant improvement in the colitis. These results suggest that the OXA-induced colitis model in the BALB/C strain provides a new way to evaluate the efficacy of therapeutic agents for UC.

The ClpXP ATP-dependent protease regulates flagellum synthesis in Salmonella enterica serovar typhimurium.

The ClpXP protease is a member of the ATP-dependent protease family and plays a dynamic role in the control of availability of regulatory proteins and the breakdown of abnormal and misfolded proteins. The proteolytic activity is rendered by the ClpP component, while the substrate specificity is determined by the ClpX component that has ATPase activity. We describe here a new role of the ClpXP protease in Salmonella enterica serovar Typhimurium in which ClpXP is involved in the regulation of flagellum synthesis. Cells deleted for ClpXP show "hyperflagellate phenotype," exhibit overproduction of the flagellar protein, and show a fourfold increase in the rate of transcription of the fliC encoding flagellar filament. The assay for promoter activity of the genes responsible for expression of the fliC showed that the depletion of ClpXP results in dramatic enhancement of the expression of the fliA encoding sigma factor final sigma(28), leaving the expression level of the flhD master operon lying at the top of the transcription hierarchy of flagellar regulon almost normal. These results suggest that the ClpXP may be responsible for repressing the expression of flagellar regulon through the control of the FlhD/FlhC master regulators at the posttranscriptional and/or posttranslational levels. Proteome analysis of proteins secreted from the mutant cells deficient for flhDC and clpXP genes demonstrated that the DeltaflhD mutation abolished the enhanced effect by DeltaclpXP mutation on the production of flagellar proteins, suggesting that the ClpXP possibly defines a regulatory pathway affecting the expression of flagellar regulon that is dependent on FlhD/FlhC master regulators.