Academic Journal

Macrophage‐dependent TGFBI‐mediated regulation of collagen levels following ingestion of apoptotic cells

التفاصيل البيبلوغرافية
العنوان: Macrophage‐dependent TGFBI‐mediated regulation of collagen levels following ingestion of apoptotic cells
المؤلفون: Nacu, Natalia, Luzina, Irina G, Todd, Nevins W, Atamas, Sergei P
المساهمون: National Institutes of Health
المصدر: The FASEB Journal ; volume 22, issue S1 ; ISSN 0892-6638 1530-6860
بيانات النشر: Wiley
سنة النشر: 2008
المجموعة: Wiley Online Library (Open Access Articles via Crossref)
الوصف: Inflammation resolution involves phagocytic clearance of apoptotic cells coinciding with activation of repair that includes accumulation of extracellular matrix. The regulation of collagen levels by macrophages during this process has not been studied. Collagen levels were increased in co‐cultures of primary fibroblasts with monocyte‐derived but not with alveolar macrophages following ingestion of apoptotic cells; direct contact between macrophages and fibroblasts was not required for collagen upregulation. Macrophages produced TGF‐β at the levels that were lower than those required for a significant upregulation of collagen, but the levels of TGF‐β‐induced (TGFBI), mRNA and protein were increased in monocyte‐derived but not alveolar macrophages following ingestion of apoptotic cells. Fibroblast activation with recombinant TGFBI led to decreased DNA binding by p53, increased DNA binding by PU.1, downregulation of matrix metalloproteinase 14 (MMP14) levels, and upregulation of collagen protein but not mRNA levels. Overexpression of p53 or MMP14, or siRNA‐mediated inhibition of PU.1 increased MMP14 and decreased collagen levels. In conclusion, following ingestion of apoptotic cells, monocyte‐derived but not alveolar macrophages produce TGFBI that employs p53 and PU.1 to downregulate MMP14, leading to a subsequent collagen accumulation. Support: NIH NHLBI 1R01HL074067 and VA Merit (SPA).
نوع الوثيقة: article in journal/newspaper
اللغة: English
DOI: 10.1096/fasebj.22.1_supplement.1072.8
الاتاحة: http://dx.doi.org/10.1096/fasebj.22.1_supplement.1072.8
Rights: http://onlinelibrary.wiley.com/termsAndConditions#vor
رقم الانضمام: edsbas.49A6B0A8
قاعدة البيانات: BASE
الوصف
DOI:10.1096/fasebj.22.1_supplement.1072.8