Y. Tsunemi, H. Saeki, K. Tamaki
Aug 1, 2012
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International Journal of Dermatology
Abstract
fibroblasts Dear Editor, Cetirizine hydrochloride (cetirizine) has a potent, selective, and long-acting H1-receptor blocking action. Double-blind, randomized, placebo-controlled studies have shown cetirizine to be effective in improving the cutaneous symptoms and pruritus of atopic dermatitis (AD), as well as in reducing the duration and amount of topical corticosteroids used in the treatment of AD. These effects can be partially attributed to its antihistamine activity, because histamine is one of the substances causing itch in AD. However, cetirizine exerts a number of anti-inflammatory activities in addition to its antihistamine ability. These anti-inflammatory properties may explain some of the clinical improvement brought about in AD by treatment with the drug. CC chemokine ligand (CCL) 17 is a Th2-type chemokine that is highly implicated in the pathogenesis of allergic disorders, especially AD. Epidermal keratinocytes and dermal fibroblasts are capable of producing CCL17. However, little is known about the inhibitory effects of cetirizine on CCL17 production. In this context, we investigated the effect of cetirizine on the production of CCL17 by HaCaT cells, the human epidermal keratinocyte cell line, and normal human dermal fibroblasts. HaCaT cells were a generous gift from Dr. T. Kuroki (Showa University, Tokyo, Japan) with the permission of Dr. N. E. Fusenig [Institute für Zellund Tumourbiologie, Deutsches Krebsforschungszentrum (Institute for Cell and Tumor Biology, German Cancer Research Center), Heidelberg, Germany]. Normal human dermal fibroblasts (Clonetics ) were obtained from Lonza Walkersville, Inc. (Walkersville, MD, USA). These cells were grown routinely in Eagle’s minimum essential medium (MEM; Sigma-Aldrich Corp., St Louis, MO, USA) with 10% fetal calf serum (FCS). After incubation in MEM without FCS for 24 hours, cytokines were added as follows: 0.5 ng/ml of recombinant human tumor necrosis factor-a (TNF-a; PeproTech, Inc., Rocky Hill, NJ, USA) and 0.5 ng/ml of recombinant human interferon-c (IFN-c; PeproTech, Inc.) for HaCaT cells, and 0.5 ng/ml of TNF-a and 0.5 ng/ml of recombinant human interleukin-4 (IL-4; PeproTech, Inc.) for fibroblasts. Cetirizine (UCB Japan Co. Ltd, Tokyo, Japan) was applied together with the cytokines. Supernatants were harvested after 48 hours and CCL17 concentrations were measured by enzymelinked immunosorbent assay (ELISA, Human CCL17/ TARC Quantikine ELISA Kit; R&D Systems, Inc., Minneapolis, MN, USA). Data were analyzed using the Mann–Whitney U-test. The CCL17 concentration in the supernatant from HaCaT cells was very low without cytokine stimulation and increased with combined stimulation by TNF-a and IFN-c, but was significantly suppressed by 10, 10, 10 and 10 M cetirizine (Fig. 1). That from fibroblasts was also very low without stimulation and increased when stimulated with TNF-a and IL-4 but was significantly suppressed by 10, 10, and 10 M cetirizine (Fig. 2). Some antihistamine drugs, such as olopatadine hydrochloride and fexofenadine hydrochloride, exert a suppressive effect on CCL17 production from peripheral blood leukocytes. However, no data are available on the inhibitory effects of cetirizine on CCL17 production. Keratinocytes and fibroblasts are major component cells of the cutaneous tissue. Thus, the control of chemokine production from these cells is one of the promising strategies for the treatment and prevention of inflammatory skin diseases.