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KMID : 0606920100180040463
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Biomolecules & Therapeutics
2010 Volume.18 No. 4 p.463 ~ p.468
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Effects of Anti-B7.1/B7.2 Antibodies on LPS-Stimulated Macrophages
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Won Tae-Joon
Huh Yoon-Joo
Lim Young-Tae
Song Dong-Sup
Hwang Kwang-Woo
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Abstract
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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-α, IL-1β, and IL-12 in LPS-activated RAW264.7 macrophage-like cells and peritoneal macrophages. Moreover, anti-B7.1/B7.2 antibodies inhibited IκBα 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.
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KEYWORD
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Anti-B7.1/B7.2 antibodies, RAW264.7, Peritoneal macrophage, Co-stimulatory molecule, Pro-inflammatory cytokine
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