BACKGROUND/AIMS: Oral administration of dextran sulfate sodium (DSS) has been reported to induce colitis in mice. The purpose of this study was to determine whether the possible pathogenic mechanism involved the acquired immune system. METHODS: Normal BALB/c and related C.B17 severe combined immunodeficient mice were fed 5% DSS (40 kilodaltons) in their drinking water for 7 days; controls were fed only water. Colons were scored for histological activity at various times. Cytokine production by cultures of colon and of draining lymph node cell was measured. The effect of DSS on the proliferation of the MCA-38 colonic epithelial cell line was assessed. RESULTS: DSS feeding resulted in a very reproducible acute distal colitis in both BALB/c and C.B17 severe combined immunodeficient mice. The lesions of BALB/c mice had an increased production of macrophage-derived cytokines, such as interleukin (IL) 1 beta, IL-6, tumor necrosis factor, and granulocyte-macrophage colony-stimulating factor, but not the T-cell cytokines IL-3 or interferon gamma. Draining lymph node cells produced these cytokines plus interferon gamma and IL-3. DSS inhibited MCA-38 cells at doses that would be easily achieved in the distal colon. CONCLUSIONS: Acute DSS-induced colitis does not require the presence of T cells or B cells because it occurred in C.B17 severe combined immunodeficient mice that lack these cells. Its induction may result from a toxicity of DSS for colonic epithelial cells.
BACKGROUND/AIMS: Oral administration of dextran sulfate sodium (DSS) has been reported to induce colitis in mice. The purpose of this study was to determine whether the possible pathogenic mechanism involved the acquired immune system. METHODS: Normal BALB/c and related C.B17 severe combined immunodeficientmice were fed 5% DSS (40 kilodaltons) in their drinking water for 7 days; controls were fed only water. Colons were scored for histological activity at various times. Cytokine production by cultures of colon and of draining lymph node cell was measured. The effect of DSS on the proliferation of the MCA-38 colonic epithelial cell line was assessed. RESULTS:DSS feeding resulted in a very reproducible acute distal colitis in both BALB/c and C.B17 severe combined immunodeficientmice. The lesions of BALB/c mice had an increased production of macrophage-derived cytokines, such as interleukin (IL) 1 beta, IL-6, tumornecrosis factor, and granulocyte-macrophage colony-stimulating factor, but not the T-cell cytokines IL-3 or interferon gamma. Draining lymph node cells produced these cytokines plus interferon gamma and IL-3. DSS inhibited MCA-38 cells at doses that would be easily achieved in the distal colon. CONCLUSIONS: Acute DSS-induced colitis does not require the presence of T cells or B cells because it occurred in C.B17 severe combined immunodeficientmice that lack these cells. Its induction may result from a toxicity of DSS for colonic epithelial cells.
Authors: Robert Barrett; Xiaolan Zhang; Hon Wai Koon; Michelle Vu; Jyh-Yau Chang; Nicole Yeager; Mary Ann Nguyen; Kathrin S Michelsen; Dror Berel; Charalabos Pothoulakis; Stephan R Targan; David Q Shih Journal: Am J Pathol Date: 2011-12-02 Impact factor: 4.307
Authors: Sandra M Ocampo; Carolina Romero; Anna Aviñó; Joan Burgueño; Miguel A Gassull; Jordi Bermúdez; Ramon Eritja; Ester Fernandez; Jose C Perales Journal: Mol Ther Date: 2011-11-01 Impact factor: 11.454
Authors: Stefan Wirtz; Vanessa Popp; Markus Kindermann; Katharina Gerlach; Benno Weigmann; Stefan Fichtner-Feigl; Markus F Neurath Journal: Nat Protoc Date: 2017-06-01 Impact factor: 13.491