Increased mucosal nitric oxide production in ulcerative colitis is mediated in part by the enteroglial-derived S100B protein

被引：102

作者：

Cirillo, C. ^{[1
]}

Sarnelli, G. ^{[1
]}

Esposito, G. ^{[2
]}

Grosso, M. ^{[3
]}

Petruzzelli, R. ^{[3
]}

Izzo, P. ^{[3
]}

Cali, G. ^{[4
]}

D'Armiento, F. P. ^{[5
]}

Rocco, A. ^{[1
]}

Nardone, G. ^{[1
]}

Iuvone, T. ^{[6
]}

Steardo, L. ^{[2
]}

Cuomo, R. ^{[1
]}

机构：

[1] Univ Naples Federico II, Dept Clin & Expt Med, Gastroenterol Unit, I-80131 Naples, Italy

[2] Univ Roma La Sapienza, Dept Human Physiol & Pharmacol V Erspamer, Rome, Italy

[3] Univ Naples Federico II, Dept Biochem & Med Biotechnol, I-80131 Naples, Italy

[4] Univ Naples Federico II, CNR, IEOS, Dept Cellular & Mol Biol & Pathol L Califano, I-80131 Naples, Italy

[5] Univ Naples Federico II, Pathol Unit, Dept Morphol & Funct Sci, I-80131 Naples, Italy

[6] Univ Naples Federico II, Dept Expt Pharmacol, I-80131 Naples, Italy

来源：

NEUROGASTROENTEROLOGY AND MOTILITY | 2009年 / 21卷 / 11期

关键词：

enteric glia; nitric oxide; S100B; ulcerative colitis; ENTERIC NERVOUS-SYSTEM; GLIAL-CELLS; CROHNS-DISEASE; RAGE; ACTIVATION; RELEASE; PROGRESSION; MODULATION; EXPRESSION; PLASTICITY;

D O I：

10.1111/j.1365-2982.2009.01346.x

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

P>In the central nervous system glial-derived S100B protein has been associated with inflammation via nitric oxide (NO) production. As the role of enteroglial cells in inflammatory bowel disease has been poorly investigated in humans, we evaluated the association of S100B and NO production in ulcerative colitis (UC). S100B mRNA and protein expression, inducible NO synthase (iNOS) expression, and NO production were evaluated in rectal biopsies from 30 controls and 35 UC patients. To verify the correlation between S100B and NO production, biopsies were exposed to S100B, in the presence or absence of specific receptor for advanced glycation end-products (RAGE) blocking antibody, to measure iNOS expression and nitrite production. S100B and iNOS expression were evaluated after incubation of biopsies with lipopolysaccharides (LPS) + interferon-gamma (IFN-gamma) in the presence of anti-RAGE or anti-S100B antibodies or budesonide. S100B mRNA and protein expression, iNOS expression and NO production were significantly higher in the rectal mucosa of patients compared to that of controls. Exogenous S100B induced a significant increase in both iNOS expression and NO production in controls and UC patients; this increase was inhibited by specific anti-RAGE blocking antibody. Incubation with LPS + IFN-gamma induced a significant increase in S100B mRNA and protein expression, together with increased iNOS expression and NO production. LPS + IFN-gamma-induced S100B up-regulation was not affected by budesonide, while iNOS expression and NO production were significantly inhibited by both specific anti-RAGE and anti-S100B blocking antibodies. Enteroglial-derived S100B up-regulation in UC participates in NO production, involving RAGE in a steroid insensitive pathway.

引用

页码：1209 / +

页数：11

共 42 条

[1] S100B-stimulated NO production by BV-2 microglia is independent of RAGE transducing activity but dependent on RAGE extracellular domain [J].