RESUMO
The Regenerating gene (REG) Ialpha protein, a trophic and/or anti-apoptotic factor, is important in the pathophysiology of gastrointestinal inflammation. Interleukin (IL)-22 is a recently identified cytokine that is suggested to have pivotal roles in inflammatory bowel diseases. We therefore investigated the involvement of the IL-22/REG Ialpha axis and examined the mechanism of regulation of REG Ialpha expression by IL-22 stimulation in ulcerative colitis (UC) mucosa. Expression of IL-22, IL-22 receptor 1 (IL-22R1), and REG Ialpha in UC mucosa was analyzed by real-time RT-PCR and immunohistochemistry. The effects of IL-22 on REG Ialpha protein expression were examined using a small-interfering RNA for STAT3, an MAPK inhibitor or a PI3K inhibitor. The element responsible for IL-22-induced REG Ialpha promoter activation was determined by a promoter deletion and electrophoretic mobility shift assay. The expression of IL-22 was enhanced in infiltrating inflammatory cells, and that of IL-22R1 and REG Ialpha was concurrently enhanced in the inflamed epithelium in UC mucosa. The levels of REG Ialpha and IL-22 mRNA expression were strongly correlated, and the distributions of REG Ialpha- and IL-22R1-positive epithelial cells were very similar. IL-22 simulation enhanced the expression of REG Ialpha protein through STAT3 tyrosine phosphorylation in colon cancer cells. The IL-22-responsive element was located between -142 and -134 in the REG Ialpha promoter region. REG Ialpha protein may have a pathophysiological role as a biological mediator for immune cell-derived IL-22 in the UC mucosa.
Assuntos
Colite Ulcerativa/metabolismo , Interleucinas/metabolismo , Litostatina/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Colite Ulcerativa/fisiopatologia , Neoplasias do Colo/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Mucosa Intestinal/metabolismo , Litostatina/genética , Sistema de Sinalização das MAP Quinases , Masculino , Pessoa de Meia-Idade , Fosforilação , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Mensageiro/metabolismo , Receptores de Interleucina/metabolismo , Fator de Transcrição STAT3/metabolismo , Adulto Jovem , Interleucina 22RESUMO
A 26-year-old woman, who had had Turner syndrome from age 10 years old, had diarrhea, fever, joint pain, and erythema in the lower left leg. She was given a diagnosis of Crohn's disease, erythema nodosum, and Hashimoto disease. Systemic steroid therapy was very effective for both intestinal and skin lesions. It has been reported that half of inflammatory bowel disease patients with Turner syndrome have 46XiX (q) type chromosome abnormality, and this case also has this type of abnormality.
