Analysis of the pathogenesis of inflammatory bowel disease using experimental colitis induced by a murine retrovirus

利用小鼠逆转录病毒诱导的实验性结肠炎分析炎症性肠病的发病机制

• 批准号: 10670457
• 负责人: NARISAWA Rintaro
• 金额: $ 1.92万
• 依托单位: NIIGATA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 1999
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10670457/
• 关键词: Ulcerative colitis; Experimental colitis; Murine AIDS; Murine leukemia virus LP-BM5; Sjoegren's syndrome; Macrophage; Cytokine; LP-BM5マウス白血病ウイルス; 炎症性腸疾患; 漬瘍性大腸炎; 動物モデル; B6ヌードマウス

BACKGROUND : LP-BM5 murine leukemia virus (MuLV) is known to induce murine AIDS (MAIDS). We have shown that sjogren's syndrome (SjS) -like exocrinopathy can be induced in mice with MAIDS and that adoptive transfer of spleen cells from MAIDS mice can induce inflammatory bowel disease-like colitis as well as SjS-like exocrinopathy in nude mice. AIM : To assess the role of interferon (IFN)-g and interleukin (IL)-10 in the pathogenesis of our experimental model, we tried to identify the cells producing these cytokines and their localization in the colitis lesions in situ. METHODS : Four-week-old C57BL/6 (B6) mice were inoculated intraperitoneally with LP-BM5 MuLV.Eight weeks after infection, lymph node cells prepared from the virus-infected mice were transferred to B6 nude mice. Four to six weeks after the cell transfer, mice with clinical symptoms such as diarrhea, anal bleeding and body weight loss were killed to examine their colons. Expression of mRNA for IFN-g and IL-10 was assessed b … More y RTPCR, and protein expression of these cytokines was also analyzed in frozen sections of colon by double color-staining immunofluorescence (IF). RESULTS : All of the mice inoculated with MAIDS lymph node cells showed colitis as well as systemic exocrinopathy, and died within 6 weeks after cell transfer. Scattered erosions of the colon were observed. CD4+ cells were dominant and distributed diffusely within the mucosal and submucosal layers. A few CD8+ cells were detected among the intraepithelial lymphocytes of the colon. Mac-1+ cells were usually localized diffusely within the lamina propria and characteristically detected beneath the injured epithelial cells. B220+cells were localized within lymph follicles. An increase of IFN- g and IL-10 mRNA was detected in the colon of mice with colitis, but not in that of control mice. Double color IF showed that Mac-1+ cells were positive for IFN-g or IL-10 and that most CD4+ cells were positive for IL-10, although the population of IFN-g-positive CD4+ cells was low.CONCLUSIONS : In our experimental colitis model, Mac-1+ macrophages which produce both IFN-g and IL-10 might play a crucial role in the pathogenesis of colitis in combination with CD4+ T cells. Less

背景：已知LP-BM 5小鼠白血病病毒（MuLV）可诱导小鼠AIDS（MAIDS）。我们已经表明，干燥综合征（SjS）样外分泌蛋白病可以在MAIDS小鼠中诱导，并且MAIDS小鼠脾细胞的过继转移可以在裸鼠中诱导炎性肠病样结肠炎以及SjS样外分泌蛋白病。目的：为了评估干扰素（IFN）-g和白细胞介素（IL）-10在我们的实验模型的发病机制中的作用，我们试图确定产生这些细胞因子的细胞及其在原位结肠炎病变中的定位。方法：用LP-BM 5 MuLV腹腔接种4周龄的C57 BL/6（B6）小鼠。感染8周后，将从病毒感染小鼠制备的淋巴结细胞转移到B6裸鼠中。细胞转移后4 - 6周，将出现腹泻、肛门出血和体重减轻等临床症状的小鼠处死，以检查其结肠。B评估IFN-γ和IL-10的mRNA表达 ...更多信息 y RTPCR，免疫荧光双染色法检测结肠冰冻切片中细胞因子的蛋白表达。研究结果：所有接种MAIDS淋巴结细胞的小鼠均表现出结肠炎以及全身性外分泌物病，并在细胞转移后6周内死亡。观察到结肠散在糜烂。CD 4+细胞占优势，弥漫分布于粘膜和粘膜下层。在结肠上皮内淋巴细胞中检测到少量CD 8+细胞。Mac-1+细胞通常弥漫定位在固有层内，并在受损的上皮细胞下方检测到特征性。B220+细胞定位于淋巴滤泡内。IFN-γ和IL-10 mRNA在结肠炎小鼠的结肠中检测到增加，而在对照小鼠的结肠中未检测到。结论：在我们的实验性结肠炎模型中，产生IFN-g和IL-10的Mac-1+巨噬细胞可能与CD 4 + T细胞联合在结肠炎的发病机制中起重要作用。少

项目成果

H Suriki: "Adoptively transferred T lymplhocytes of mice infected with a murine retrovirus induced proctitis in syngeneic nu/un mice." Gastroenterology. 114. G4478 (1998)

H Suriki：“过继转移感染鼠逆转录病毒的小鼠的 T 淋巴细胞，在同系 nu/un 小鼠中诱发直肠炎。”

馬場靖幸 ら: "マウスレトロウイルスによる実験性腸炎における5-ASA(Mesalazine)の治療効果およびその作用機序の解析"消化器と免疫. 36. 78-81 (1999)

Yasuyuki Baba等：“5-ASA（美沙拉嗪）对小鼠逆转录病毒引起的实验性肠炎的治疗效果及其作用机制的分析”胃肠道和免疫学36. 78-81（1999）。

H. Suriki: "Adoptively transferred T lymphocytes of mice infected with a murine retrovirus induced proctitis in syngeneic nu/nu mice"Gastroenterology. 114. G4478 (1998)

H. Suriki：“感染鼠逆转录病毒的小鼠过继转移 T 淋巴细胞，在同系 nu/nu 小鼠中诱导直肠炎”胃肠病学。

佐々木俊哉 ら: "マウスレトロウイルスにより惹起されるシエーグレン症候群様外分泌腺症におけるサイトカイン発現の検討"消化器と免疫. 35. 141-144 (1998)

Toshiya Sasaki 等：“小鼠逆转录病毒诱导的齐格伦综合征样外分泌腺病中细胞因子表达的检查”《胃肠道和免疫学》35. 141-144 (1998)。

Hidehisa Suriki et al.: "Analysis of cytokine production in the colon of nude mice with experimenatal colitis induced by adoptive transfer of immunocompetent cells from mice infected with a murine retrovirus"Clinical Immunology. 97. 33-42 (2000)

Hidehisa Suriki 等人：“通过过继转移感染鼠逆转录病毒的小鼠的免疫活性细胞诱导的患有实验性结肠炎的裸鼠结肠中细胞因子产生的分析”临床免疫学。