大腸炎モデル
↓大腸CD169+Mφソーティング 8
0 1 2 3
Maf
0 5 10 15
Ccl8
0 20 40 60
Slpi
0 1 2 3 4
Slc7a11
Day 0 4 8 0 4 8 0 4 8 0 4 8
5
* * *n.s. * *
0 1 2 3
Ctrl AcOH Maf
0 5 10 15 20
Ctrl AcOH Ccl8
0 2 4 6
Ctrl AcOH Slpi
0 3 6 9
Ctrl AcOH Slc7a11
Fold change
0 (h)
↑ 4% AcOH
注腸
大腸CD169+↓Mφソーティング
酢酸誘導
4大腸炎モデル
* * * *
a
b
Fold change
炎症急性期 炎症収束期
Maf ON
応答遺伝子急性炎症
Nrf2 OFF 組織保護遺伝子
酸化ストレス
Maf OFF 応答遺伝子急性炎症
Nrf2 ON
組織保護遺伝子 形質変化
図 9
図9. 大 腸マ ク ロ フ ァ ー ジ は Maf発 現の 減少に よ り 形 質 を変え る
(a) DSS 誘 導大 腸炎 モ デ ル のタイ ムコー ス（上）と 、野生 型 マ ウ ス に お け る CD64+ CD169+マ ク ロ フ ァ ー ジ の遺 伝子発 現 レベル を qRT-PCR に よ り定量し た（ 下 ）。n=7 (Day0), n=8 (Day4, 8)/グル ープで解 析を行な っ た 。*p<0.05, n.s., not significant, one-way ANOVA. (b) 酢酸 誘 導大 腸炎 モ デ ル のタイ ムコー ス（上）と 、野生 型 マ ウ ス に お け るCD64+ CD169+マ ク ロ フ ァ ー ジ の遺 伝子発 現をqRT-PCRに よ り定量し た（ 下 ）。 n=8/グル ープで解 析を行な っ た 。(a, b) 縦軸に は腸炎 を 誘 導 し な い マ ウ ス の CD64+ CD169+マ ク ロ フ ァ ー ジ の遺 伝子発 現に 対 す る相対値を 示 し た 。*p<0.05, n.s., not significant, Student’s t-test. (a,b) 平均値とSEMをグ ラフ に 示 し た 。(c) 大 腸マ ク ロ フ ァ ー ジ の 形 質 転 換 メ カ ニ ズ ム を 示 し た模 式図 。腸 内細菌の よ う な外来 抗 原 を感知し たCD169+マ ク ロ フ ァ ー ジ は 、Maf依存的 に 急 性 炎 症 応 答遺 伝子発 現 レベル が亢進 す る 。一 方 、Nrf2活 性 を 阻 害 す る こ と で 組 織保 護 遺 伝子 の遺 伝子発 現を 抑 制 す る 。好 中球 が 産 生 す る 活 性 酸 素 の よ う に 、 炎 症 に伴っ て 生じた 酸 化 ス トレス を マ ク ロ フ ァ ー ジ が感知す る と 、同じCD169+マ ク ロ フ ァ ー ジ に お い て 、Maf発 現 レベル が 減弱し 、 Nrf2依存的 な 組 織保 護 遺 伝子 の発 現を 促 進 す る 。
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