Y Yanagihara

Publications (2)16.79 Total impact

• Article: Atopy and the human IL-4 receptor alpha chain.

  K Izuhara, Y Yanagihara, N Hamasaki, T Shirakawa, J M Hopkin
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  ABSTRACT: Atopy is a common inherited disorder characterized by increased IgE responsiveness, but no functional analysis of the candidate genes related to atopy has been performed. IL-4 is important for B-cell production of IgE, and the human IL-4 receptor alpha chain (hIL-4Ralpha) is crucial for the binding and signal transduction of IL-4, so hIL-4Ralpha may be a candidate gene related to atopy. We examined the relationship between the variation at amino acid 50 of hIL-4Ralpha and atopic asthma. We performed a genetic study to investigate the relationship between the variation of amino acid 50 (isoleucine [Ile(50)] or valine [Val(50)]) and atopic asthma in a Japanese population and a functional study with the use of transfectants that expressed hIL4Ralpha bearing either Ile(50) or Val(50). Furthermore, we analyzed CD23 expression and IgE synthesis after IL-4 stimulation of peripheral blood mononuclear cells bearing either Ile(50) or Val(50). The prevalence of Ile(50) was higher than that of Val(50) in individuals with atopic asthma, especially during childhood. In transfectants, germline epsilon transcription activity and Stat6 activity were upregulated by the Ile(50) variant, compared with Val(50), but receptor affinity for IL-4 was similar between the two. CD23 expression and IgE synthesis in response to IL-4 were augmented in Ile(50)-expressing peripheral mononuclear blood cells compared to cells expressing Val(50). The Ile(50) variant of hIL-4Ralpha may be related to atopic asthma, particularly in children.
  Journal of Allergy and Clinical Immunology 08/2000; 106(1 Pt 2):S65-71. · 11.00 Impact Factor
• Article: Cutting edge: dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis.

  H Mitsuyasu, Y Yanagihara, X Q Mao, P S Gao, Y Arinobu, K Ihara, A Takabayashi, T Hara, T Enomoto, S Sasaki, M Kawai, N Hamasaki, T Shirakawa, J M Hopkin, K Izuhara
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  ABSTRACT: Two variants of the IL-4R alpha-chain (IL-4Ralpha) gene have been recently identified in association with different atopic disorders. To clarify the etiological relationship between the two variants, we analyzed responsiveness to IL-4 of transfectants with four kinds of IL-4Ralpha carrying either Val or Ile at 50 and either Gln or Arg at 551. The substitution of Ile for Val augmented STAT6 activation, proliferation, and transcription activity of the Iepsilon promoter by IL-4, whereas that of Arg for Gln did not change these IL-4 signals. Arg551 was not associated with atopic asthma in the Japanese population. CD23 expression and IgE synthesis by IL-4 were augmented in Ile50-bearing PBMC, compared with those bearing Val50. Taken together, substitution of Arg551 does not enhance the IL-4 signal for generation of germline epsilon transcript, whereas the substitution of Ile50 contributes to enhancement of IgE synthesis.
  The Journal of Immunology 03/1999; 162(3):1227-31. · 5.79 Impact Factor