Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Effects of Anti-B7.1/B7.2 Antibodies on LPS-Stimulated Macrophages

  • Won, Tae-Joon (Cellular and Molecular Immunology Lab., College of Pharmacy, Chung-Ang University) ;
  • Huh, Yoon-Joo (Cellular and Molecular Immunology Lab., College of Pharmacy, Chung-Ang University) ;
  • Lim, Young-Tae (Cellular and Molecular Immunology Lab., College of Pharmacy, Chung-Ang University) ;
  • Song, Dong-Sup (Cellular and Molecular Immunology Lab., College of Pharmacy, Chung-Ang University) ;
  • Hwang, Kwang-Woo (Cellular and Molecular Immunology Lab., College of Pharmacy, Chung-Ang University)
  • Received : 2010.07.23
  • Accepted : 2010.10.04
  • Published : 2010.10.31
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Abstract

T-cell activation depends on signals received by the T-cell receptor and CD28 co-stimulatory receptor. Since B7.1 and B7.2 molecules expressed on the surface of antigen presenting cells provide co-stimulatory signals through CD28 to T-cells, an inhibitor of CD28-B7.1/B7.2 binding has been proposed as a therapeutic agent for suppression of excessive T-cell activity. Although anti-B7.1/B7.2 antibodies are known to block B7.1 and B7.2 molecules, their effects on intracellular events in antigen presenting cells remain unclear. In this study, anti-B7.1/B7.2 antibodies decreased secretion of nitric oxide and pro-inflammatory cytokines such as TNF-$\alpha$, IL-$1{\beta}$, and IL-12 in LPS-activated RAW264.7 macrophage-like cells and peritoneal macrophages. Moreover, anti-B7.1/B7.2 antibodies inhibited $I{\kappa}B{\alpha}$ phosphorylation and down-regulated expression of co-stimulatory molecules including B7.1, B7.2, and PD-L1 in LPS-stimulated peritoneal macrophages. These findings suggest that CTLA4-Ig and anti-B7.1/B7.2 antibodies may be candidates to treat chronic inflammatory diseases and autoimmune responses caused by excessive activation of both T-cells and macrophages.

Keywords

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