title: Intestinal mononuclear cells primed by systemic interleukin-12 display long-term ability to aggravate colitis in mice.
abstract: To address whether the burst of systemic interleukin-12 (IL-12) influences intestinal inflammation elicited by luminal stimuli, we induced IL-12 release by cDNA injection in C57BL/6 mice and simultaneously started dextran sulphate sodium administration. The sequence of the inflammatory response triggered by IL-12 release was characterized by assessing myeloperoxidase activity and histological damage in colon samples on days 1, 3, 5 and 7 after colitis induction. To evaluate the persistence of IL-12 priming, colitis was induced in mice 7 or 60 days after cDNA injection. Under IL-12 influence, the development of acute colitis presented a faster and selective infiltration of inflammatory mononuclear cells in the lamina propria. Recruitment was driven by systemic cytokines rather than luminal antigens. Interestingly, when colitis was triggered 7 or 60 days after the cytokine storm, cells maintained the ability to worsen clinical signs of intestinal inflammation. Together, a systemic IL-12 burst effectively primed intestinal cells that became more prone to develop inflammatory responses. Activation was long-lasting because intestinal cells maintained their inflammatory potential and their ability to aggravate colitis.
authors.affiliation: Immunology, Department of Clinical Biochemistry-CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Luciano P
authors.initials: LP
authors.lastname: Pedrotti
authors.affiliation: Immunology, Department of Clinical Biochemistry-CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Angela A
authors.initials: AA
authors.lastname: Sena
authors.affiliation: Immunology, Department of Clinical Biochemistry-CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: María Cecilia
authors.initials: MC
authors.lastname: Rodriguez Galán
authors.affiliation: Immunology, Department of Clinical Biochemistry-CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Hugo
authors.initials: H
authors.lastname: Cejas
authors.affiliation: Immunology, Department of Clinical Biochemistry-CIBICI (CONICET), Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Córdoba, Argentina.
authors.forename: Silvia G
authors.initials: SG
authors.lastname: Correa
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003092:Colitis / Q000139:chemically induced / Q000276:immunology*; D003106:Colon / Q000276:immunology*; D018076:DNA, Complementary / Q000008:administration & dosage; D016264:Dextran Sulfate; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D053765:Interleukin-12 Subunit p35 / Q000235:genetics*; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D007413:Intestinal Mucosa / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D019444:Vaccines, DNA / Q000276:immunology
chemical_list: D018076:DNA, Complementary; D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D011993:Recombinant Fusion Proteins; D019444:Vaccines, DNA; D016264:Dextran Sulfate
keywords: colitis; interleukin-12; macrophage; priming; systemic T cell