| 1115 Effect of S100b on superoxide production by PMN in diabetes | ||
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Y. UCHIDA1, A. KANTARCI2, Y. DING3, E.L. BATISTA, Jr.2, H. HASTURK2, H. KURIHARA4, and T.E. VAN DYKE2, 1Boston University, Goldman School of Dental Medicine, MA, USA, 2Boston University, MA, USA, 3Boston University, boston, MA, USA, 4Hiroshima University Graduate School of Biomedical Sciences, Japan S100b is a member of the S100 protein family, which is a calcium binding protein with chemotactic activity for polymorphonuclear leukocytes (PMN) and monocytes. Previous work has shown that S100b is produced by the inflammatory tissues and may play role in stimulating phagocytic activity. S100b may also act extracellularly through its ability to activate the receptor for advanced glycation end products (RAGE). However, the function of S100b mediated RAGE activation in PMN is currently unknown. Objective: The aim of this study was to elucidate the effects of S100b on superoxide release from PMN. Methods: PMN were isolated from peripheral blood. Superoxide generation was measured by the SOD inhibitable cytochrome C reduction assay. PMN were stimulated with S100b and were treated with N-formyl-methionyl-leucyl-phenylalanine (fMLP; 2.5 μM) or phorbol 12-myristate 13-acetate (PMA; 200 nM). Expression of RAGE in PMN was investigated by using RT-PCR and Western blotting. Results: Normal PMN treated with S100b (1μg/ml) produced significantly higher superoxide in response to fMLP (177 pmol O2-/106cells/min) compared to untreated cells (p<0.01). Likewise, PMA treatment resulted in significantly increased superoxide generation from non-diabetic PMN (252 pmol O2-/106cells/min) compared to cells that were not treated with S100b (p<0.01). PCR and Western blotting experiments showed that expression of RAGE in diabetic human PMN was higher than in normal cells both at mRNA and protein levels. S100b (1μg/ml) treatment of diabetic PMN produced significantly higher superoxide in response to fMLP (522 pmol O2-/106cells/min) or PMA (502 pmol O2-/106cells/min) compared to normal cells treated with fMLP (p<0.001). Conclusions: S100b upregulates the production of superoxide anion by PMN. PMN of diabetic patients produce more superoxide than PMN of healthy people. Destruction of periodontal tissue in diabetics could be related to a RAGE-mediated increase in PMN function. Supported by USPHS Grant DE13191 and GCRC Grant MO1 RR00533 | ||
| Seq #129 - Periodontal Research Pathogenesis 1 2:00 PM-4:00 PM, Thursday, 10 March 2005 Baltimore Convention Center Exhibit Hall E-F | ||
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