JP5442185B2 - 感作性物質評価方法 - Google Patents
感作性物質評価方法 Download PDFInfo
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- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Description
IL−2Rは、ヒト脳内皮細胞において、IL−2のシグナルを伝え、T細胞増殖活性に関わる(非特許文献9)。
この場合、上記哺乳動物細胞の中でも、血液、骨髄細胞を用いることが好ましい。
この場合、上記培養細胞の中でも、THP−1及び/又はU−937を用いることが好ましい。
RPMI1640(GIBCO社製)に10%FBS、100units/mLペンシリン(Sigma社製)と100μg/mLストレプトマイシン(ベーリンガー社製)を加えて調整した。
強い感作性を示す物質として、1−クロロ−2,4−ジニトロベンゼン(DNCB,Sigma社製)とp−ベンゾキノン(BQ,Sigma社製)を用い、それぞれ、2.5mg/mL、3.0mg/mLとなるようにDMSOに溶解し用いた。
弱い感作性を示す物質としては、硫酸ニッケル(Ni,Sigma社製)とオイゲノール(EU,Sigma社製)を用い、それぞれ、20mg/mL、15mg/mLとなるように生理食塩水に溶解し用いた。
培地中のTHP−1(American Type Culture Collectionから分譲)に、それぞれの終濃度が、DNCBは5.0μg/mL、BQは6.0μg/mL、Niは200μg/mL、EUは150μg/mLとなるように添加し、CO2インキュベーター中で、37℃にて8時間培養した。また、コントロールとして、被験物質を添加しない未適用対照を設けた。
培養終了後、細胞よりTORIZOL(invitrogen社製)にて細胞を溶解することによって総RNAを抽出し、cDNAラベル化キット(GEヘルスケア社製)を用いてRT−PCR法にて、RNAから蛍光ラベル化されたcDNAを合成した。合成したcDNAをInteligene Human Cytokinechip Ver3.1(Takara社製)に、60℃にて、16時間ハイブリダイズした。ハイブリダイズ終了後、蛍光スキャナ(ScanArray Gx,PerkinElmer社製)にて各遺伝子の発現量を測定し、コントロールと各被験物質間の発現差を解析ソフト(ScanArray Express Ver3.0,PerkinElmer社製)により解析した。
各被験物質を添加した細胞における遺伝子発現量/コントロールの遺伝子発現量=相対発現量
比較例として、非感作性物質としてラウリル硫酸ナトリウム(SLS,Sigma社製)を5.0mg/mLにて生理食塩水に溶解し、50μg/mLとなるように細胞に添加し、実施例1と同様の実験を行った。
実施例1及び比較例1により評価した遺伝子の中から、強い感作性物質(DNCB、BQ)、弱い感作性物質(Ni、EU)及び非感作性物質(SLS)に対して、コントロールと比較して発現が変化したものを解析した。
遺伝子の変化(発現量)が、コントロールと比較して2.0倍以上であった場合を「+++」、1.5倍以上2.0倍未満であった場合を「++」、1.2倍以上1.5倍未満であった場合を「+」、1.2倍未満であった場合を「−」とし、表1に示した。
その結果、強い感作性物質(DNCB、BQ)のみに対して、遺伝子の変化(発現量)が、コントロールと比較して1.5倍以上(「++」、「+++」の変化)であった遺伝子について、2種類(遺伝子No.1〜2)を見出した。弱い感作性物質(Ni、EU)のみに対して、遺伝子の変化(発現量)が、コントロールと比較して1.5倍以上(「++」、「+++」の変化)であった遺伝子について、1種(遺伝子No.3)を見出した。その他の変化しなかった遺伝子4種類(遺伝子No.4〜7)に関しては、反応なし群として表1に示した。
Claims (1)
- 哺乳動物のTHP−1、U−937、KG−1、MUTZ−1、HL−60、Jurkatから1種以上選択される培養細胞と被験物質とをインキュベートし、当該細胞のインターロイキン−8(IL−8)及びIL−2受容体(IL−2R)の発現量を測定し、当該発現量を対照の発現量と比較することを特徴とする、被験物質の感作性を評価する方法。
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WO2011078778A1 (en) * | 2009-12-22 | 2011-06-30 | Biovator Technologies Ab | Method for assessing the sensitisation capability of a compound |
WO2012002507A1 (ja) * | 2010-07-01 | 2012-01-05 | 国立大学法人東北大学 | 多色発光細胞を用いた免疫毒性評価システム |
US20150038511A1 (en) | 2012-08-09 | 2015-02-05 | Celgene Corporation | Treatment of immune-related and inflammatory diseases |
PL2882441T3 (pl) | 2012-08-09 | 2020-09-21 | Celgene Corporation | Leczenie chorób immunologicznych i zapalnych |
JP2017522270A (ja) | 2014-05-19 | 2017-08-10 | セルジーン コーポレイション | 全身性エリテマトーデスの治療のための3−(4−((4−(モルホリノメチル−ベンジル)オキシ)−1−オキソイソインドリン−2−イル)ピペリジン−2,6−ジオン |
CA3017270A1 (en) * | 2016-03-23 | 2017-09-28 | Senzagen Ab | Method for determining the skin sensitizing potency of an agent and arrays for use in the same |
GB201700138D0 (en) | 2017-01-05 | 2017-02-22 | Senzagen Ab | Analytical methods and arrays for use in the same |
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SE506533C2 (sv) * | 1995-07-03 | 1998-01-12 | Birger Andersson | En process för in vitro analys av substansers toxiska och allergena egenskaper samt användning av neopterin för att skilja mellan allergiska immunreaktioner |
AU782044B2 (en) * | 1999-10-15 | 2005-06-30 | Novozymes A/S | A method for the assessment of allergenicity |
JP4270702B2 (ja) * | 2000-02-07 | 2009-06-03 | 株式会社資生堂 | 感作性物質のインビトロ評価法 |
JP2004222582A (ja) * | 2003-01-22 | 2004-08-12 | Kao Corp | 感作性評価方法 |
JP2006311858A (ja) * | 2005-04-05 | 2006-11-16 | Shiseido Co Ltd | 感作性物質のinvitro評価方法及びそれに用いる遺伝子工学的に作製された細胞 |
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