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1.
Langenbecks Arch Surg ; 395(4): 429-35, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19277698

RESUMO

BACKGROUND AND AIMS: Adrenal hormones influence inflammatory and fibrotic activity and thereby are involved in wound-healing process. Any excess as well as any shortage of glucocorticoids leads to a delayed wound healing. Mineralocorticoids like aldosterone have a pro-fibrotic and pro-inflammatory impact; thus, reduction of circulating aldosterone should result in an attenuated inflammatory response to implanted foreign bodies. MATERIAL AND METHODS: Eighteen rats were bilaterally adrenalectomized and substituted with dexamethasone (12 microg/kg per day) and 1% salt in their drinking water; 22 rats were sham-operated. The surgical suture material was removed after 3 weeks and analyzed for size of granuloma, ratio of collagen type I/III, apoptotic cells (terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling), expression of matrix metalloproteinase (MMP)-2, cyclooxygenase 2, tumor necrosis factor receptor 2 (TNF-R2), cluster of differentiation 68 (CD68), Ki67, and cold shock protein Y box binding protein 1 (YB-1). Cell expression was scored according to Remmele. RESULTS: All animals developed foreign body granulomas around the sutures. Absence of circulating aldosterone after adrenalectomy (ADX) was associated with smaller granuloma size and a reduced ratio of collagen type I/III. Ki67 and MMP-2 showed the strongest expression in cells of the infiltrate around suture. In adrenalectomized rats, we observed significantly less CD68-positive macrophages and less Ki67-positive cells but no significant differences in the expression of YB-1, TNF-R2, or MMP-2. Looking for correlations and co-expressions of proteins, the number of significant Spearman correlations was reduced in the ADX group compared to controls (one and four, respectively). CONCLUSION: The absence of circulating aldosterone attenuates inflammatory intensity around suture material. Foreign body granuloma seems to be an appropriate model to study chronic inflammatory process.


Assuntos
Aldosterona/metabolismo , Granuloma de Corpo Estranho/metabolismo , Inflamação/metabolismo , Cicatrização/fisiologia , Adrenalectomia , Animais , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Suturas/efeitos adversos
2.
FASEB J ; 21(4): 1047-57, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17215487

RESUMO

Matrix metalloproteinase-2 (MMP-2) is a key regulator in wound healing that orchestrates tissue remodeling. In the present study the spatial and temporal distribution of MMP-2 gene transcription, protein synthesis, and enzymatic activity were analyzed following polymeric mesh (polyglactin, polypropylene) implantation in transgenic reporter mice harboring MMP-2 regulatory sequences -1686/+423 or -1241/+423. Polymers induced MMP-2 promoter activity in macrophages within the foreign body granuloma via sequences -1686/+423 with concomitantly up-regulated protein synthesis and enzymatic activity. Macrophages distant from mesh filaments exhibited low MMP-2 expression levels. Fibroblasts surrounding mesh material displayed strong MMP-2 gene transcription independent of the included promoter sequences, whereas fibroblasts without close contact to mesh material had low MMP-2 synthesis rates due to silencing activity of sequences -1686/-1241. In vitro studies support a cellular crosstalk concept, as macrophages trans-repressed MMP-2 gene transcription in fibroblasts. The zonal and cell-specific regulation of MMP-2 gene transcription illuminates an intimate cellular crosstalk in foreign body reaction that may provide a new approach for mesh modification.


Assuntos
Fibroblastos/metabolismo , Regulação Enzimológica da Expressão Gênica , Macrófagos/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Polímeros/química , Animais , Materiais Biocompatíveis/química , Granuloma/metabolismo , Masculino , Camundongos , Camundongos Transgênicos , Células NIH 3T3 , Regiões Promotoras Genéticas , Transcrição Gênica , Cicatrização
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