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Kang, Tae, Lee, Kim, Moon, and Kim: Protease-activated Receptor 2 is Associated with Activation of Human Macrophage Cell Line THP-1
Original Article

Immune Network 2005; 5(4): 193-198.

Published online: 31 December 2005

DOI: https://doi.org/10.4110/in.2005.5.4.193

Protease-activated Receptor 2 is Associated with Activation of Human Macrophage Cell Line THP-1

Chon-Sik Kang1, 3, Jin Tae1, Young-Mi Lee1, Byeong-Soo Kim2, Woo-Sung Moon4, Dae-Ki Kim3

1Department of Oriental Pharmacy, College of Pharmacy, Wonkwang University, Iksan, Korea.

2Department of Companion and Laboratory Animal Science, Kongju National University, Gongju, Korea.

3Department of Immunology, Chonbuk National University Medical School, Jeonju, Korea.

4Department of Pathology, Chonbuk National University Medical School, Jeonju, Korea.

Correspondence to: Dae-Ki Kim, Department of Immunology, Chonbuk National University Medical School, 664-14 Deokjin-dong 1-ga, Deokjin-gu, Jeonju 561-756, Korea. (Tel) 82-63-270-3080, (Fax) 82-63-274-9833, deakim@chonbuk.ac.kr

Copyright © 2005 The Korean Association of Immunologists

(open-access):

This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

Protease-activated receptor 2 (PAR2) belongs to a family of G protein-coupled receptors activated by proteolytic cleavage. Trypsin-like serine proteases interact with PAR2 expressed by a variety of tissues and immune cells. The aim of our study was to investigate whether PAR2 stimulation can lead to the activation of human macrophages.

Methods

PAR2-mediated proliferation of human macrophage cell line THP-1 was measured with MTT assay. We also examined the extracellular regulated kinase (ERK) phosphorylation and cytokine production induced by trypsin and PAR2-agonist using western blot and enzyme-linked immunosorbent assay (ELISA), respectively.

Results

Treatment of trypsin or PAR2-activating peptide increased cell proliferation in a dose-dependent manner, and induced the activation of ERK1/2 in THP-1 cells. In addition, trypsin-induced cell proliferation was inhibited by pretreatment of an ERK inhibitor (PD98059) or trypsin inhibitor (SBTI). Moreover, PAR2 activation by trypsin increased the secretion of TNF-α in THP-1 cells.

Conclusion

There results suggest that PAR2 activation by trypsin-like serine proteases can induce cell proliferation through the activation of ERK in human macrophage and that PAR2 may play a crucial role in the cell proliferation and cytokine secretion induced by trypsin-like serine proteases.

Keywords: Protease-activated receptor 2, macrophage, trypsin, cell proliferation, extracellular regulated kinase

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