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| Pine bark extract pycnogenol downregulates IFN-gamma-induced adhesion of T cells to human keratinocytes by inhibiting inducible ICAM-1 expression |
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| Author(s): Bito T, Roy S, Sen CK, Packer L |
| Source: FREE RADICAL BIOLOGY AND MEDICINE Volume: 28 Issue: 2 Pages: 219-227 Published: JAN 15 2000 |
| Times Cited: 31 References: 40 |
| Abstract: Expression of intercellular adhesion molecule-1 (ICAM-1) is necessary for leukocyte/keratinocyte interactions. Upregulation of ICAM-1 expression in keratinocytes has been observed in several inflammatory dermatoses, such as psoriasis, atopic dermatitis, and lupus erythematosus. Inflammatory cytokines, such as interferon-gamma (IFN-gamma), upregulate ICAM-1 expression in keratinocytes. Because of potent antioxidant and anti-inflammatory properties of the French maritime pine bark extract, Pycnogenol (Horphag Research, Geneva, Switzerland), its effects were investigated on the interaction of T cells with keratinocytes after activation with IFN-gamma and the molecular mechanisms involved in such interactions. Studies were performed using a human keratinocyte cell line, HaCaT. Cell adhesion in the presence of IFN-gamma was studied using a coculture assay. Treatment of HaCaT cells with 20 U/ml IFN-gamma for 24 h markedly induced adherence of Jurkat T cells to HaCaT cells. PYC pretreatment (50 mu g/ml, 12 h) significantly inhibited IFN-gamma induced adherence of T cells to HaCaT cells (p < .01). ICAM-1 plays a major role in the IFN-gamma-induced adherence of T cells to keratinocytes. Thus, the effect of PYC on IFN-gamma-induced ICAM-1 expression was investigated as well. Pretreatment of HaCaT cells with PYC significantly inhibited IFN-gamma-induced expression of ICAM-1 expression in HaCaT cells. The downregulation of inducible ICAM-1 expression by PYC was both dose and time dependent. A 50 mu g/ml dose of PYC and a 12 h pretreatment time (i.e., before activation with IFN-gamma) provided maximal (similar to 70%) inhibition of inducible ICAM-1 expression in HaCaT cells. Gamma-activated sequence present on the ICAM-1 gene confers IFN-gamma responsiveness in selected cells of epithelial origin (e.g., keratinocytes) that are known to express ICAM-1 on activation with IFN-gamma. Gel-shift assays revealed that PYC inhibits IFN-gamma-mediated activation of Stat1, thus suggesting a transcriptional regulation of inducible ICAM-1 expression by PYC. These results indicate the therapeutic potential of PYC in patients with inflammatory skin disorders. (C) 2000 Elsevier Science Inc. |
| Document Type: Article |
| Language: English |
| Reprint Address: Roy, S (reprint author), Univ Calif Berkeley, Dept Mol & Cell Biol, 251 Life Sci Addit, Berkeley, CA 94720 USA |
Addresses:
1. Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA
2. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA |
| Publisher: PERGAMON-ELSEVIER SCIENCE LTD, THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND |
| Subject Category: Biochemistry & Molecular Biology; Endocrinology & Metabolism |
| IDS Number: 283MV |
| ISSN: 0891-5849 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |