Neutrophil derived human S100A12 (EN-RAGE) is strongly expressed during chronic active inflammatory bowel disease.
نویسندگان
چکیده
BACKGROUND Intestinal inflammation in Crohn's disease (CD) and ulcerative colitis (UC) is characterised by an influx of neutrophils into the intestinal mucosa. S100A12 is a calcium binding protein with proinflammatory properties. It is secreted by activated neutrophils and interacts with the multiligand receptor for advanced glycation end products (RAGE). Promising anti-inflammatory effects of blocking agents for RAGE have been reported in murine models of colitis. AIMS To investigate expression and serum concentrations of S100A12 in inflammatory bowel disease (IBD). METHODS We performed immunohistochemical studies and immunofluorescence microscopy in biopsies from patients with CD and UC. S100A12 serum concentrations were analysed using a sandwich ELISA. RESULTS Immunohistochemical studies revealed profound expression of S100A12 in inflamed intestinal tissue from IBD patients whereas no expression was found in tissue from healthy controls. Staining for S100A12 during chronic active CD and UC was restricted to infiltrating neutrophils. Serum S100A12 levels were significantly elevated in patients with active CD (470 (125) ng/ml; p<0.001, n=30) as well as those with active UC (400 (120) ng/ml; p<0.01, n=15) compared with healthy controls (75 (15) ng/ml; n=30). Even in inactive disease, elevated serum concentrations were found, at least in CD. S100A12 levels were well correlated with disease activity in CD and UC. CONCLUSIONS We demonstrated that neutrophil derived S100A12 is strongly upregulated during chronic active IBD, suggesting an important role during the pathogenesis of IBD. Serum S100A12 may serve as a useful marker for disease activity in patients with IBD.
منابع مشابه
Expression of Pro-inflammatory Protein S100A12 (EN-RAGE) in Behçet's Disease and Its Association with Disease Activity: A Pilot Study
BACKGROUND S100A12 is a member of the S100 family of calcium-binding proteins and is secreted either in inflamed tissues or in the bloodstream by activated neutrophils. Expression of S100A12 has been reported in various diseases, especially non-infectious inflammatory diseases, such as Kawasaki disease, giant cell arteritis and inflammatory bowel disease. OBJECTIVE This study was conducted to...
متن کاملExpression of the pro-inflammatory protein S100A12 (EN-RAGE) in rheumatoid and psoriatic arthritis.
OBJECTIVES Infiltration of synovial tissue by neutrophils is crucial in rheumatoid arthritis (RA), psoriatic arthritis (PsA) and seronegative arthritis (SA). Altered vascular function and endothelial activation are important in PsA. S100A12 (EN-RAGE) is secreted by activated granulocytes and binds to the receptor for advanced glycation end products, which induces nuclear factor (NF)-kappaB-depe...
متن کاملPReS-FINAL-2182: The role of murine rage in innate immune responses and inflammation: a systematic approach
Introduction The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor expressed on various cells which interacts with a diverse class of ligands, e.g. ‘danger signals’ such as neutrophil-derived S100A12. RAGE has been implicated in the pathogenicity of various inflammatory diseases. However, the exact role of RAGE has not been sufficiently defined. Our recent data on S...
متن کاملSerum S100A12 (EN-RAGE) levels in patients with decreased renal function and subclinical chronic inflammatory disease.
BACKGROUND The calcium-binding protein S100A12 (EN-RAGE) causes inflammation through interaction with the multiligand receptor for advanced glycation end products (RAGE). The aim of the study was to determine S100A12 levels and describe their relationship to inflammatory markers in patients with decreased renal function. METHODS The studied group consisted of 46 patients with various degrees ...
متن کاملVascular remodeling and arterial calcification are directly mediated by S100A12 (EN-RAGE) in chronic kidney disease.
BACKGROUND The proinflammatory cytokine S100A12 (also known as EN-RAGE) is associated with cardiovascular morbidity and mortality in hemodialysis patients. In the current study, we tested the hypothesis that S100A12 expressed in vascular smooth muscle in nonatherosclerosis-prone C57BL/6J mice on normal rodent chow diet, but exposed to the metabolic changes of chronic kidney disease (CKD), would...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Gut
دوره 52 6 شماره
صفحات -
تاریخ انتشار 2003