J Korean Med Sci.  2008 Oct;23(5):857-863. 10.3346/jkms.2008.23.5.857.

The Effect of Interleukin-4 and Amphiregulin on the Proliferation of Human Airway Smooth Muscle Cells and Cytokine Release

• Shim JY
• Park SW
• Kim DS
• Shim JW
• Jung HL
• Park MS

• KMID: 1783073
• DOI: http://doi.org/10.3346/jkms.2008.23.5.857

Abstract

Airway smooth muscle (ASM) hyperplasia and angiogenesis are important features associated with airway remodeling. We investigated the effect of IL-4 and amphiregulin, an epidermal growth factor family member, on the proliferation of human ASM cells and on the release of vascular endothelial growth factor (VEGF) and monocyte chemotactic protein (MCP)-1 from human ASM cells. Human ASM cells were growth-arrested for 48 hr and incubated with platelet-derived growth factor (PDGF)- BB, interleukin (IL)-4, amphiregulin, and VEGF to evaluate cell proliferation. The cells were treated with PDGF, IL-4 and amphiregulin to evaluate the release of VEGF, MCP-1. IL-4 suppressed unstimulated and PDGF-stimulated ASM cell proliferation. Amphiregulin stimulated ASM cell proliferation in a dose-dependent manner. VEGF did not have any influence on ASM cell proliferation. IL-4 stimulated VEGF secretion by the ASM cells in a dose-dependent manner and showed added stimulatory effects when co-incubated with PDGF. Amphiregulin did not promote VEGF secretion. IL-4 and amphiregulin showed no stimulatory effects on MCP-1 secretion. The results of this study showed that IL-4 had bifunctional effects on airway remodeling, one was the suppression of the proliferation of the ASM cells and the other was the promotion of VEGF release by the ASM cells, and amphiregulin can promote human ASM cell proliferation.

Keyword

Interleukin-4; Remodeling; Humans, Bronchi; Myocytes, Smooth Muscle; Cell Proliferation; Vascular Endothelial Growth Factor; Amphiregulin

MeSH Terms

Bronchi/metabolism
Cell Proliferation
Cells, Cultured
Chemokine CCL2/metabolism
Chemokine CCL3/metabolism
Cytokines/metabolism
*Gene Expression Regulation
Glycoproteins/*physiology
Humans
Intercellular Signaling Peptides and Proteins/*physiology
Interleukin-4/metabolism/*physiology
Models, Biological
Myocytes, Smooth Muscle/*metabolism
Vascular Endothelial Growth Factor A/metabolism