TGF-β1-mediated regulation of thymus and activation-regulated chemokine (TARC/CCL17) synthesis and secretion by HaCaT cells co-stimulated with TNF-α and IFN-γ

Zheng, Xueyi; Nakamura, Koichiro; Tojo, Michiko; Oyama, Noritaka; Nishibu, Akiko; Satoh, Masataka; Kakinuma, Takashi; Wakugawa, Motoshi; Tamaki, Kunihiko; Kaneko, Fumio

« Previous Next »Journal of Dermatological Science
Volume 30, Issue 2 , Pages 154-160, November 2002

TGF-β₁-mediated regulation of thymus and activation-regulated chemokine (TARC/CCL17) synthesis and secretion by HaCaT cells co-stimulated with TNF-α and IFN-γ

Xueyi Zheng
- Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan
Koichiro Nakamura
- Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan
- Corresponding author. Tel.: +81-24-548-2111x2403; fax: +81-24-548-5412
Michiko Tojo
- Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan
Noritaka Oyama
- Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan
Akiko Nishibu
- Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan
Masataka Satoh
- Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan
Takashi Kakinuma
- Department of Dermatology, University of Tokyo, Tokyo, Japan
Motoshi Wakugawa
- Department of Dermatology, University of Tokyo, Tokyo, Japan
Kunihiko Tamaki
- Department of Dermatology, University of Tokyo, Tokyo, Japan
Fumio Kaneko
- Department of Dermatology, Fukushima Medical University School of Medicine, Hikarigaoka 1, Fukushima 960-1295, Japan

Received 20 March 2002; received in revised form 24 June 2002; accepted 26 June 2002.

Abstract

Thymus and activation-regulated chemokine (TARC/CCL17) contributes not only to the recruitment of leukocytes, but is also involved in immune disorders, such as atopic dermatitis (AD) and bronchial asthma. We have previously reported that the levels of TARC were high in patients with AD and that lesional epidermis were strongly immunoreactive for TARC. In this paper, the effects of transforming growth factor (TGF)-β₁ on the expression of TARC/CCL17 were examined in HaCaT cells, a human keratinocytes (KCs) cell line, co-stimulated with TNF-α and IFN-γ. We found that TGF-β₁ down-regulated the TARC synthesis and secretion of HaCaT cells co-stimulated with TNF-α and IFN-γ in a dose-dependent manner. TGF-β₁ at a concentration of 10ng/ml maximally inhibited this secretion. Northern blot analysis showed a similar inhibitory effect of TGF-β₁ on TARC mRNA expression by HaCaT cells. The TGF-β₁-induced down-regulation of TARC/CCL17 in HaCaT cells suggests that TGF-β₁ might regulate the TARC-related inflammatory processes, which may be important for understanding the pathogenesis of allergic diseases.

Keywords: Chemokines, Keratinocytes, Thymus and activation-regulated chemokine/CCL17, Transforming growth factor-β₁

Abbreviations: TGF-β₁, transforming growth factor-β₁, TARC, thymus and activation-regulated chemokine, IFN-γ, interferon-γ, TNF-α, tumor necrosis factor-α, KCs, keratinocytes