Activation of inflammatory cells and cytokines by peptide epitopes in vitro: a simple in-vitro screening assay for prioritizing them for in-vivo studies

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• 作者：Lakshmi A. Mundkur (1)
  Meenakshi Varma (1)
  Hemapriya Shivanandan (1)
  Dhanush Krishna (1)
  Kiran Kumar (1)
  Xinjie Lu (2)
  Vijay. V. Kakkar (1) (2)
  
• 关键词：Atherosclerosis ; Inflammation ; Dendritic cells ; T ; regulatory cells ; Cytokines ; Vaccine
• 刊名：Inflammation Research
• 出版年：2013
• 出版时间：May 2013
• 年：2013
• 卷：62
• 期：5
• 页码：471-481
• 全文大小：892KB
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• 作者单位：Lakshmi A. Mundkur (1)
  Meenakshi Varma (1)
  Hemapriya Shivanandan (1)
  Dhanush Krishna (1)
  Kiran Kumar (1)
  Xinjie Lu (2)
  Vijay. V. Kakkar (1) (2)
  
  1. Thrombosis Research Institute, Narayana Hrudayalaya, 258/A, Bommasandra Industrial Area, Anekal Taluk, Bangalore, India
  2. Thrombosis Research Institute, London, UK
  
• ISSN：1420-908X

文摘

Objective Antigen-specific immune modulation is an attractive approach to atherosclerosis treatment. The aim of this study was to develop an in-vitro assay to screen peptide molecules for their inflammatory propensity. Materials Human dendritic cells derived from CD14+ monocytes were activated using peptides derived from apolipoprotein B100 (ApoB), heat shock protein 60 (HSP60) and complement cascade (peptide A) in vitro, and used for priming autologous T cells. Proliferation of T cells, their differentiation to regulatory cells (Treg) and their cytokine profile were studied. The efficacy of the peptides in preventing atherosclerosis was studied in ApoBtm2Sgy/Ldlrtm1Her/J knockout mice. Results and conclusion ApoB and HSP60 peptides induced T-cell proliferation and expansion of regulatory T cells with interleukin-10 and transforming growth factor-β secretion. In comparison, peptide A was a poor stimulator of T cells and was found to induce tumor necrosis factor-α secretion by activated T cells. ApoB and HSP60 peptides were found to reduce early atherosclerotic lesion formation in mice by 32.1 and 33.5?%, respectively, while the reduction with peptide A was 5.7?%. Thus the in-vitro assay shows an apparent correlation with in-vivo activity and can be developed as a screening assay to prioritize the candidate molecules for animal efficacy testing.