Format

Send to

Choose Destination
See comment in PubMed Commons below
Atherosclerosis. 2010 Dec;213(2):429-35. doi: 10.1016/j.atherosclerosis.2010.08.064. Epub 2010 Aug 26.

DPP-4 (CD26) inhibitor alogliptin inhibits TLR4-mediated ERK activation and ERK-dependent MMP-1 expression by U937 histiocytes.

Author information

1
Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC 29401, United States.

Abstract

Dipeptidyl peptidase-4 (DPP-4)/CD26, a cell surface glycoprotein, is expressed by a variety of cells including T cells, B cells, NK cells, and macrophages. Although it has been shown that DPP-4/CD26 is involved in T cell activation, its role in biological functions in macrophages has not been well investigated. In this study, we used alogliptin, a specific inhibitor of DPP 4/CD26, to study the effect of DPP-4/CD26 on the activation of the extracellular signal-regulated kinase (ERK) that plays a critical role in the expression of proinflammatory cytokines and matrix metalloproteinases (MMPs) in U937 histiocytes. Results showed that 1nM of alogliptin inhibited ERK phosphorylation induced by lipopolysaccharide (LPS), a ligand for toll-like receptor (TLR)4, by 91%. Furthermore, results showed that alogliptin inhibited LPS-stimulated MMP-1 expression in a concentration-dependent manner and 1nM of alogliptin inhibited MMP-1 expression by 60%. To confirm the involvement of the ERK pathway in MMP-1 expression by U937 cells, we showed that PD98059, a specific inhibitor for the ERK pathway, blocked LPS-stimulated MMP-1 expression. In addition to MMP-1, our study showed that alogliptin also inhibited MMP-9, -12 and -15, but had no effect on TIMP-1 and -2 expression. Taken together, this study showed for the first time that the inhibition of DPP-4/CD26 by alogliptin suppressed TLR4-mediated ERK activation and ERK-dependent MMP expression by U937 cells, suggesting that DPP-4/CD26 may play an important role in macrophage-mediated inflammation response and tissue remodeling.

[Indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center