JP2018083776A - 粘膜型マスト細胞への分化抑制用組成物 - Google Patents
粘膜型マスト細胞への分化抑制用組成物 Download PDFInfo
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Abstract
本発明の目的は、食事の用に供することができ、かつ、細胞あたりの粘膜型マスト細胞の割合を減少させることができる組成物を提供することにある。
【解決手段】
上記目的は、しょうゆ中のエタノール可溶性成分を有効成分として含有する、粘膜型マスト細胞への分化抑制用組成物及び抗アレルギー用組成物により解決される。これらの組成物によれば、有効成分による粘膜型マスト細胞への分化を抑制する作用及び抗アレルギー作用を通じて、粘膜性のアレルギーや該アレルギーと関連する炎症、例えば、食物アレルギー、花粉症、胃炎、腸炎、下痢、潰瘍性大腸炎、鼻炎、気管支炎、気管支喘息、レフレル症候群、口内炎などによる症状や自己免疫症状を改善、緩和、抑制、治療若しくは予防すること、又は免疫療法の用に供することが期待できる。
【選択図】図3A
Description
[1]しょうゆ中のエタノール可溶性成分を有効成分として含有する、粘膜型マスト細胞への分化抑制用組成物。
[2]前記エタノール可溶性成分は、5vol%以上の含水エタノール可溶性成分である、[1]に記載の粘膜型マスト細胞への分化抑制用組成物。
[3]前記エタノール可溶性成分は、5vol%の含水エタノール可溶性成分及び/又は99vol%以上の含水エタノール可溶性成分である、[1]に記載の粘膜型マスト細胞への分化抑制用組成物。
[4]前記エタノール可溶性成分は、水不溶性のエタノール可溶性成分である、[1]〜[3]のいずれか1項に記載の粘膜型マスト細胞への分化抑制用組成物。
[5]前記粘膜型マスト細胞への分化抑制用組成物は、5vol%の含水エタノール抽出物及び/又は99vol%以上の含水エタノール抽出物である、[1]〜[4]のいずれか1項に記載の粘膜型マスト細胞への分化抑制用組成物。
[6]前記組成物は、インターロイキン−3及びインターロイキン−10の存在下で、未成熟マスト細胞株から粘膜型マスト細胞への分化を抑制する作用を有する組成物である、[1]〜[5]のいずれか1項に記載の粘膜型マスト細胞への分化抑制用組成物。
[7][1]〜[6]のいずれか1項に記載の組成物を有効成分として含有する、抗アレルギー用組成物。
[8]前記抗アレルギー用組成物は、食物アレルギーを発症している者又は食物アレルギーを発症する可能性がある者に摂取される抗アレルギー用組成物である、[7]に記載の抗アレルギー用組成物。
[9]前記抗アレルギー用組成物は、食物性アレルゲンを含有する食品と併用される抗アレルギー用組成物である、[7]又は[8]に記載の抗アレルギー用組成物。
[10]前記抗アレルギー用組成物は、粘膜組織を介するアレルギーを対象とする抗アレルギー用組成物である、[7]〜[9]のいずれか1項に記載の抗アレルギー用組成物。
SIGMA社製Dulbecco’s Modified Eagle’s培地に、下記の終濃度になるように試薬を添加して、培地を調製した。
10%(w/v) FBS
1%(w/v) Penicilline/Streptomycin
2mM L−glutamine
0.05mM 2−mercaptoethanol
10%(w/v) Rat T−STIM(日本ベクトン・ディッキンソン社製)
MC/9(ATCC CRL−8306)凍結ストックを培地に添加し、週に2回程度培地を交換しながら培養した。5継代(P5)の時点で3×106 cells/mLのワーキングストックを作成した。ワーキングストックを培地に添加し、培養後週に2回程度で継代しながら培養することにより、P9以降の細胞を回収した。回収した細胞について、培地で1回洗浄した後、トリパンブルー(Gibco社製)で懸濁し血球計算板を用いて細胞数を計測した。その後、2×106 cells/mLになるように培地に懸濁することにより、MC/9細胞懸濁液を調製した。
mouse recombinant protein IL−3(100μM;eBioscience社製)及びmouse recombinant protein IL−10(100μM;eBioscience社製)を、それぞれ120ng/mlとなるように培地で希釈して、IL−3溶液及びIL−10溶液を調製した。
下記に示すスキーム(I)により例1〜例4の被験試料を調製した。
例5〜例15の被験試料を調製するために、しょうゆ分画を下記のように実施した。
96ウェル平底プレート(BD FALCON社製)の各ウェルに、内容物が下記に示す所定の最終濃度になるように例1〜15の被験試料及び培地を添加して、初発細胞数を1.0×105cells/wellとし、それぞれ30ng/mlのIL−3及びIL−10の存在下で3日間培養した。ただし、上記培地として、Rat T−STIMを含有しない培地を用いた。
例1の被験試料の希釈倍率:20倍、60倍、120倍、240倍、480倍、960倍
例2の被験試料の希釈倍率:30倍、60倍、120倍、240倍、480倍、960倍
例3及び例4の被験試料の希釈倍率:15倍、30倍、60倍、120倍、240倍、480倍、960倍
例5〜例10の被験試料の希釈倍率:120倍
例11の被験試料の希釈倍率:60倍、120倍、240倍、480倍、960倍、1,920倍及び3,840倍
例12〜例13の被験試料の希釈倍率:60倍、120倍、240倍、480倍、960倍
例14〜例15の被験試料の希釈倍率:60倍、120倍、240倍、480倍、960倍、1,920倍及び3,840倍
培養後に回収した細胞を、1×PBS/2%FBSで2回洗浄した後、Fcブロック(BD Bioscience社製)と反応させた。次いで、反応後の細胞を、PE標識anti−mouse FcεRIα(Biolegend社製)及びPE/cy7標識anti−mouse CD117(c−Kit)(Biolegend社製)と反応させた。次いで、反応後の細胞を、1×PBSで1回洗浄した後、Fixable Viability Dye eFluor 450(eBioscience社製)と反応させた。
図1A及び1Bが示すとおり、上清(1)に含まれる成分として、50vol%のエタノール濃度にて溶解するしょうゆ中の成分は、MMCP−1陽性細胞の割合及び数を濃度依存的に低下させる活性を有することが確認できた。一方で、沈殿物(2)に含まれる成分として、50vol%の濃度のエタノールでは溶解せずに、さらに水にも溶解しないしょうゆ中の成分は、そのような活性を有していないことが確認できた(図1A〜1Cを参照)。
上記例1〜例4の結果より、しょうゆのエタノール抽出物はMMCP−1陽性細胞への分化抑制作用を有することがわかった。そこで、カラムに吸着させたしょうゆ中の成分をグラジエント的にエタノールで溶出し、どの画分がMMCP−1陽性細胞への分化抑制作用を有するかを評価した。
図2の結果より、D−IV以降の画分集合物に、MMCP−1陽性細胞への分化抑制活性を有する成分が集中して存在する可能性が示唆された。そこで、画分集合物D−IV、E−I、E−II、F及びGについて、様々な濃度に希釈して培養液に添加し、MMCP−1陽性細胞への分化抑制活性を評価した。その結果、画分集合物D−IV、F及びGは、MMCP−1陽性細胞の割合及び数を濃度依存的に低下させる活性を有することが確認できた(図3A及び3Bを参照)。その一方で、総細胞数への影響はなかった(図3Cを参照)。このうち、画分集合物D−IV及びGは、MMCP−1陽性細胞の割合を濃度依存的に低下させる活性が顕著であった。
例5〜例15(画分集合物A〜G)の被験試料について、UV吸収スペクトル分析機であるVientoXS(DSファーマバイオメディカル社製)を用いて、波長220nm、280nm及び440nmのUV吸収スペクトルを測定した結果を図4に示す。
例6〜例15(画分集合物B〜G)の被験試料について、「バイオ・ラッド プロテインアッセイ」(バイオ・ラッド社製)を用いて、タンパク質濃度を測定した結果を表1に示す。表1の結果より、MMCP−1陽性細胞への分化抑制作用がみられる画分集合物D−IV、F及びGについては、60wt%以上のタンパク質を含有するものであることがわかった。
Claims (7)
- しょうゆ中のエタノール可溶性成分を有効成分として含有する、粘膜型マスト細胞への分化抑制用組成物。
- 前記エタノール可溶性成分は、5vol%以上の含水エタノール可溶性成分である、請求項1に記載の粘膜型マスト細胞への分化抑制用組成物。
- 前記エタノール可溶性成分は、5vol%の含水エタノール可溶性成分及び/又は99vol%以上の含水エタノール可溶性成分である、請求項1に記載の粘膜型マスト細胞への分化抑制用組成物。
- 前記エタノール可溶性成分は、水不溶性のエタノール可溶性成分である、請求項1〜3のいずれか1項に記載の粘膜型マスト細胞への分化抑制用組成物。
- 前記粘膜型マスト細胞への分化抑制用組成物は、しょうゆの5vol%の含水エタノール抽出物及び/又はしょうゆの99vol%以上の含水エタノール抽出物である、請求項1〜4のいずれか1項に記載の粘膜型マスト細胞への分化抑制用組成物。
- 前記組成物は、インターロイキン−3及びインターロイキン−10の存在下で、未成熟マスト細胞株から粘膜型マスト細胞への分化を抑制する作用を有する組成物である、請求項1〜5のいずれか1項に記載の粘膜型マスト細胞への分化抑制用組成物。
- 請求項1〜6のいずれか1項に記載の組成物を有効成分として含有する、抗アレルギー用組成物。
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