RESUMO
BACKGROUND: Under inflammatory conditions with strong oxidative stresses, advanced glycation end-products (AGE), carbonyl compounds, are produced. The concentration of pentosidine, an AGE, reportedly correlates with complications of diabetes mellitus and worsening of rheumatoid arthritis, but its role in the pathogenesis of inflammatory bowel diseases (IBD) is unclear. METHODS: Immunohistochemistry was performed with antibodies against pentosidine, and 8-OH-2-deoxyguanosine. The urinary concentration of pentosidine was also quantified by enzyme-linked immunosorbent assay method. RESULTS: Pentosidine expression was up-regulated in the inflamed tissue of IBD. The expression of both pentosidine and 8-OH-2-deoxyguanosine was similar and increased in the inflamed epithelium and infiltrating cells (neutrophils and lymphocytes). The urinary concentration of pentosidine in active ulcerative colitis was significantly greater than that in inactive ulcerative colitis (0.12+/-0.15 vs 0.021+/-0.011 microg/mg of Cr, P<0.05), and was greater in active Crohn's disease than in inactive Crohn's disease (0.071+/-0.086 vs 0.039+/-0.023 microg/mg of Cr). CONCLUSIONS: The urinary pentosidine level correlated with the activity of ulcerative colitis and may be a marker for disease activity in ulcerative colitis.
Assuntos
Arginina/análogos & derivados , Colite Ulcerativa/metabolismo , Colo/química , Doença de Crohn/metabolismo , Produtos Finais de Glicação Avançada/análise , Lisina/análogos & derivados , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Arginina/análise , Arginina/urina , Colite Ulcerativa/urina , Doença de Crohn/urina , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análise , Ensaio de Imunoadsorção Enzimática , Células Epiteliais/química , Feminino , Produtos Finais de Glicação Avançada/urina , Humanos , Imuno-Histoquímica , Linfócitos/química , Lisina/análise , Lisina/urina , Masculino , Pessoa de Meia-Idade , Neutrófilos/química , Índice de Gravidade de Doença , Regulação para Cima , Adulto JovemRESUMO
Nociceptin/orphanin (Noc/oFQ), endogenous agonist for nociceptin receptor (NOR), is thought to be a stimulator of neurogenic inflammation. We investigated the possible role of Noc/oFQ in the development of colitis using NOR-deficient mice treated with dextran sulfate sodium (DSS). Colitis was significantly improved in NOR-deficient mice against wild-type mice. Expression level of mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and infiltrating cells also significantly decreased in NOR-deficient mice against wild-type mice. Nociceptin expression increased in wild-type mice after DSS treatment. These results suggest stimulation by Noc/oFQ deteriorates colonic inflammation via up-regulation of adhesion molecule.
Assuntos
Colite/metabolismo , Modelos Animais de Doenças , Peptídeos Opioides/fisiologia , Animais , Antígenos CD/metabolismo , Peso Corporal/fisiologia , Moléculas de Adesão Celular/metabolismo , Contagem de Células/métodos , Colite/induzido quimicamente , Colite/genética , Colite/patologia , Colo/patologia , Sulfato de Dextrana , Feminino , Mucosa Gástrica/citologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Regulação da Expressão Gênica/efeitos dos fármacos , Regulação da Expressão Gênica/genética , Imuno-Histoquímica/métodos , Cadeias beta de Integrinas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Mucoproteínas , Peptídeos Opioides/deficiência , Coloração e Rotulagem/métodos , Fatores de Tempo , NociceptinaAssuntos
Neoplasias do Colo/etiologia , Doença de Hodgkin/terapia , Linfoma não Hodgkin/etiologia , Segunda Neoplasia Primária/etiologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Ciclofosfamida/administração & dosagem , Feminino , Humanos , Transplante de Células-Tronco de Sangue Periférico , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Dosagem Radioterapêutica , Indução de Remissão , Vincristina/administração & dosagemAssuntos
Mucosa Gástrica/metabolismo , Ferro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Diálise Renal/efeitos adversos , Bicarbonatos/metabolismo , Ácido Gástrico/metabolismo , Mucosa Gástrica/irrigação sanguínea , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Estresse Oxidativo , Consumo de Oxigênio , Gastropatias/etiologia , Gastropatias/fisiopatologiaRESUMO
BACKGROUND AND AIM: The pathogenesis of ulcerative colitis (UC) is unclear, but abnormal infiltration of T lymphocytes in the colonic mucosa has been implicated in the mucosal tissue damage. The abnormal cytokine production because of a T helper (h)1/Th2 imbalance may play an important role in continuing inflammation in the colonic mucosa. In the present study, the expression of chemokine receptor 5 (CCR5) as a Th1 marker and a chemoattractant receptor-homologs molecule expressed on Th2 cells (CRTH2) were investigated in order to analyze impaired Th1/Th2 responses in the colonic mucosa of UC patients. METHODS: Tissue samples were obtained by colonic biopsies from patients with UC or colonic polyps, with informed consent. Immunohistochemical analysis was performed on periodate, lysine-paraformaldehyde-fixed serial cryostat sections using the labeled streptavidin biotin method. Monoclonal antibodies against CD4, CCR5 or CRTH2 were used as primary antibodies. The number of cells expressing CD4, CCR5 or CRTH2 per unit area was calculated by using an image analyzer. RESULTS: In the patients with UC, the numbers of CD4- and CCR5-positive cells were significantly increased in inflamed mucosa, and appeared to be correlated with the disease activity. The infiltration of CRTH2-positive cells was predominantly observed in the mildly inflamed or the margin of inflamed mucosa of UC patients. CONCLUSION: There is a possibility that Th1 responses significantly occur in colonic mucosa with severe inflammation, while Th2 responses mainly occur with mild inflammation in UC patients. The Th1/Th2 imbalance in colonic mucosa may be related to the disease progression of UC.