Apolipoprotein A-I inhibits the production of interleukin-1β and tumor necrosis factor-α by blocking contact-mediated activation of monocytes by T lymphocytes

作者：Nevila Hyka, Jean‐Michel Dayer, Christine Modoux, Tadahiko Kohno, Carl K. Edwards, Pascale Roux‐Lombard, Danielle Burger · 发表于：Blood · 年份：2001 · DOI：10.1182/blood.v97.8.2381 · 被引用次数：387 · 研究领域：Systemic Lupus Erythematosus Research、Atherosclerosis and Cardiovascular Diseases、Cell Adhesion Molecules Research

Tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta), essential components in the pathogenesis of immunoinflammatory diseases, are strongly induced in monocytes by direct contact with stimulated T lymphocytes. This study demonstrates that adult human serum (HS) but not fetal calf or cord blood serum displays inhibitory activity toward the contact-mediated activation of monocytes by stimulated T cells, decreasing the production of both TNF-alpha and IL-1beta. Fractionation of HS and N-terminal microsequencing as well as electroelution of material subjected to preparative electrophoresis revealed that apolipoprotein A-I (apo A-I), a "negative" acute-phase protein, was the inhibitory factor. Functional assays and flow cytometry analyses show that high-density lipoprotein (HDL)-associated apo A-I inhibits contact-mediated activation of monocytes by binding to stimulated T cells, thus inhibiting TNF-alpha and IL-1beta production at both protein and messenger RNA levels. Furthermore, apo A-I inhibits monocyte inflammatory functions in peripheral blood mononuclear cells activated by either specific antigens or lectins without affecting cell proliferation. These results demonstrate a new anti-inflammatory activity of HDL-associated apo A-I that might have modulating functions in nonseptic conditions. Therefore, because HDL has been shown to bind and neutralize lipopolysaccharide, HDL appears to play an important part in modulating both acute and chronic inflammati...