The Iron Chelator and Anticancer Agent Dp44mT Relieves Allergic Inflammation in Mice With Allergic Rhinitis
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ORIGINAL ARTICLE
The Iron Chelator and Anticancer Agent Dp44mT Relieves Allergic Inflammation in Mice With Allergic Rhinitis Hee-Yun Kim,1 Na-Ra Han,1 Hyung-Min Kim,1,3 and Hyun-Ja Jeong2,3
Our previous study showed that an iron chelator and anticancer agent Di-2pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) has an antiinflammatory effect in human mast cells. However, antiinflammatory effect of Dp44mT remains unclear in animal models. In this study, we assessed whether administration of Dp44mT could relieve clinical symptoms of ovalbumin (OVA)-induced allergic rhinitis (AR) mice. After administration of Dp44mT, number of rubs was significantly decreased, and levels of histamine and IgE were suppressed in serum of AR mice. Also, serum levels of interleukin (IL)-1β, thymic stromal lymphopoietin (TSLP), and tumor necrosis factor (TNF)-α increased by OVA challenge were significantly lowered by administration of Dp44mT. T helper type 1 (Th1) cytokine interferon-γ level was significantly increased by administration of Dp44mT, whereas Th2 cytokines such as IL-4, IL-5, and IL-13 were significantly reduced by administration of Dp44mT. In intranasal tissues of AR mice, levels of IL-1β, TSLP, TNF-α, and IL-6 and activities and protein levels of caspase-1 were significantly reduced by administration of Dp44mT. Interestingly, administration of Dp44mT reduced number of infiltrated eosinophils and mast cells through the inhibition of macrophage inflammatory protein-2 and intercellular adhesion molecule-1 in intranasal tissues of AR mice. In conclusion, these results indicate that Dp44mT also has potential antiinflammatory effects in vivo as well as in vitro.
Abstract—
KEY WORDS: allergic rhinitis; Dp44mT; anticancer agent; Th1/Th2 cytokines; inflammatory cytokine; caspase-1.
INTRODUCTION
1
Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea 2 Department of Food Science and Technology and Research Institute for Basic Science, Hoseo University, 20, Hoseo-ro 79 beon-gil, Baebangeup, Asan, Chungcheongnam-do 31499, Republic of Korea 3 To whom correspondence should be addressed to Hyung-Min Kim at Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Seoul, 130-701, Republic of Korea. E-mail: [email protected]; and Hyun-Ja Jeong at Department of Food Science and Technology and Research Institute for Basic Science, Hoseo University, 20, Hoseo-ro 79 beon-gil, Baebang-eup, Asan, Chungcheongnam-do 31499, Republic of Korea. E-mail: [email protected]
Allergic rhinitis (AR) is one of the most common types of allergy and its prevalence rate is constantly increasing [1]. Many people with AR have also allergic conjunctivitis, atopic dermatitis, or asthma [2]. AR is an IgE-mediated inflammatory reaction characterized by one or more nasal clinical symptoms including itching, rhinorrhea, nasal discharge, and sneezing [3]. AR stimulates a systemic increase of inflammation by various immune cells [4]. Within minutes of various allergens exposure, mast c
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