Articles

Article

Original

Exp Neurobiol 2004; 13(1): 57-65

Published online July 1, 2004

© The Korean Society for Brain and Neural Sciences

Transforming Growth Factor-Beta1-Induced MMP-2 Production and Chemotaxis are Suppressed by the Amyloid-Beta Peptide in Human Monocytic THP-1 Cells

Eun Ok Lee, Yoo Jung Shin and Young Hae Chong*

Department of Microbiology, College of Medicine, Division of MolecularBiology and Neuroscience, Ewha Medical Research Institute,Ewha Womans University, Seoul 158-710, Korea

Correspondence to: *To whom correspondence should be addressed.
TEL: +82-2-650-5739. FAX: +82-2-653-8891
e-mail: younghae@mm.ewha.ac.kr

Abstract

The amyloid-beta peptide (AՂ) accumulation in the brain is crucial for development of Alzheimer's disease. Expression of transforming growth factor-Ղ1 (TGF-Ղ1), an immunosuppressive cytokine, has been associated in vivo with AՂ accumulation in transgenic mice and recently with AՂ clearance by activated microglia suggesting its beneficial and deleterious effects in neuronal cells. In this study, we demonstrated that TGF-Ղ1 induced matrix metalloproteinase-2 (MMP-2) expression in time- and dose- dependent manners and enhanced MIP-1Ձ-mediated chemotaxis of human monocytic THP-1 cells. Of interest to note, we found that AՂ1-42 treatment consistently inhibited the TGF-Ղ1-induced MMP-2 production and also resulted in a marked suppression of TGF-Ղ1-mediated chemotaxis of monocytes whereas the reverse peptide, AՂ42-1, showed little effect. Furthermore, AՂ1-42 markedly suppressed the transactivation of transfected reporter construct containing TGF-Ղ-inducible response element in TGFՂ-1 treated cells. Collectively, these data suggest that AՂ1-42 might be a negative regulator of TGF-Ղ1-mediated MMP-2 induction and chemotaxis in human monocytic cells.

Keywords: AՂ,, TGF-Ղ,1, MMP-2, chemotaxis, Alzheimer's disease,