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Macrophage Migration Inhibitory Factor Homologs of Anisakis simplex Suppress Th2 Response in Allergic Airway Inflammation Model via CD4⁺CD25⁺Foxp3⁺ T Cell Recruitment¹

Sang Kyun Park^*, Min Kyoung Cho^*, Hye-Kyung Park^,, Keun Hee Lee^*, Sun Joo Lee^*, Seon Hee Choi^*, Mee Sun Ock, Hae Jin Jeong^*,, Moo Hyung Lee^* and Hak Sun Yu^2,*,

^* Department of Parasitology and Department of Internal Medicine, School of Medicine, Pusan National University Busan, Busan, Korea; Pusan National University Hospital Medical Research Institute, Busan, Korea; and Department of Parasitology, Kosin University College of Medicine, Busan, Korea

We have cloned the macrophage migration inhibitory factor (MIF)-like protein (Anisakis simplex (As)-MIF) from larvae of the whale worm (Anisakis simplex third-stage larvae). Asthma was induced in the mice using OVA/alum, with or without various concentrations of rAs-MIF treatment before OVA/alum challenge. Treatment with rAs-MIF coupled with OVA/alum during the challenge period induced a complete inhibition of eosinophilia and goblet cell hyperplasia within the lung and profoundly ameliorated the development of lung hyperreactivity. Also, rAs-MIF was shown to reduce profoundly the quantity of Th2-related cytokines (IL-4, IL-5, and IL-13) in the bronchial alveolar lavage fluid and allergen-specific IgG2a in sera. IL-10 and TGF-β levels in the bronchoalveolar lavage fluid of the rAs-MIF-treated group were significantly higher than in the other groups. Additionally, CD4⁺CD25⁺Foxp3⁺ T cells (regulatory T) were recruited to the spleen and lungs of the rAs-MIF-treated mice, but this recruitment was inhibited by anti-rAs-MIF Ab.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by the Korea Research Foundation Grant funded by the Korean government (Ministry of Education and Human Resource Development) (KRF-2006-E00087).

² Address correspondence and reprint requests to Dr. Hak Sun Yu, Department of Parasitology, School of Medicine, Pusan National University, 1-10 Ami-dong, Seo-gu, Busan 602-739, Korea. E-mail address: hsyu{at}pusan.ac.kr

³ Abbreviations used in this paper: MIF, migration inhibitory factor; T_reg, regulatory T; rMou-MIF, recombinant mouse MIF; BALF, bronchoalveolar lavage fluid; Bm-MIF, Brugia malayi MIF; Penh, enhanced pause.

⁴ The online version of this article contains supplemental material.