Epithelial overexpression of interleukin-32alpha in inflammatory bowel disease.
Interleukin (IL)-32 is a recently described proinflammatory cytokine, characterized by induction of nuclear factor (NF)-kappaB activation. We studied IL-32alpha expression in the inflamed mucosa of inflammatory bowel disease (IBD). We also investigated mechanisms regulating IL-32alpha expression. Tissue samples were obtained endoscopically or surgically from patients with ulcerative colitis (UC) (n = 10), Crohn's disease (CD) (n = 10), ischaemic colitis (n = 4) and normal colorectal tissues (n = 10). IL-32alpha expression was evaluated by standard immunohistochemical procedure. IL-32 mRNA expression was analysed by Northern blot. IL-32alpha was expressed weakly by colonic epithelial cells from normal individuals and subjects with ischaemic colitis. In the inflamed mucosa of IBD patients, epithelial IL-32alpha expression was increased markedly. In UC and CD patients, IL-32alpha expression was enhanced in affected mucosa compared to non-affected mucosa. In intestinal epithelial cell lines, expression of IL-32alpha mRNA and protein was enhanced by IL-1beta, interferon (IFN)-gamma and tumour necrosis factor (TNF)-alpha. A combination of TNF-alpha plus IFN-gamma exerted synergistic effects. IL-32alpha induction by IL-1beta and/or TNF-alpha was mediated by NF-kappaB activation. Epithelial IL-32alpha expression was increased in IBD patients, and in CD patients in particular. IL-32alpha might be involved in the pathophysiology of IBD as a proinflammatory cytokine and a mediator of innate immune response.
Shioya
M
M
Department of Medicine, Shiga University of Medical Science, Seta-Tukinowa, Otsu, Japan.
Nishida
A
A
Yagi
Y
Y
Ogawa
A
A
Tsujikawa
T
T
Kim-Mitsuyama
S
S
Takayanagi
A
A
Shimizu
N
N
Fujiyama
Y
Y
Andoh
A
A
D000328:Adult; D003106:Colon / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D005260:Female; D015870:Gene Expression; D006801:Humans; D018928:Immunity, Mucosal; D007124:Immunoenzyme Techniques; D015212:Inflammatory Bowel Diseases / Q000276:immunology*; D007378:Interleukins / Q000235:genetics / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000276:immunology*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D014407:Tumor Cells, Cultured
D016207:Cytokines; C496971:IL32 protein, human; D007378:Interleukins; D012333:RNA, Messenger