Regulation of bone marrow-derived monocytic cells and inhibition of inflammation-associated colon cancer development by chemokines and neurotransmitters
CCR2欠損マウスとCX3CR1欠損マウスの骨髄細胞を移植した骨髄キメラマウスを作成し、移植2か月後にAOM/DSSによる傷害を開始した。DSS3サイクル投与終了時点でCCR2欠損キメラマウスとWTキメラマウスの大腸を比較すると、前者は後者に比して、(1)炎症部位への単球・線維細胞の浸潤が著明に減少し、(2)これらが産生するTIMP-1も有意に減少し、(3)type 1 collagenの分解亢進により大腸線維化が抑制されていた。3サイクル投与終了10週の時点ではCCR2欠損キメラマウス、CX3CR1欠損キメラマウスともにWTキメラマウスに比して、大腸の短縮は軽減され大腸腫瘍の数は減少した。
We prepared bone marrow (BM) chimeric mice, which were reconstituted with BM cells devived from CC chemokine receptor 2 (CCR2)-deficient mice or CX3C chemokine receptor 1(CX3CR1)-deficient mice. After 2 months of BM transplantation, BM chimeric mice were treated with azoxymethane/dextran sodium sulfate(DSS). At 10 days after the third DSS treatment, in CCR2-deficient BM chimeric mice compared with in wild-type(WT) BM chimeric mice, the number of monocyted and fibrocytes in the colonic lamina propria and mRNA expression level of tissue inhibitor of metalloproteinase-1 in the colon tissue were significantly reduced, and colon fibrosis was attenuated by hyper-degradation of extracellular type Ⅰcollagen. At 10 weeks after the third DSS treatment, shortening of the colon length was dampened and the number of colon tumors was significantly reduced in both CCR2-deficient BM chimeric mice and CX3CR1-deficient BM chimeric mice compared with in WT BM chimeric mice.
ケモカインと神経伝達物質による骨髄由来単球系細胞制御と炎症関連大腸癌の発症抑制
2020RP0019
(293.11KB)
