Does the bovine lactoferrin improve chronic inflammation in the immuno-suppressive condition induced by FIV infection?

牛乳铁蛋白是否可以改善 FIV 感染引起的免疫抑制病症中的慢性炎症？

• 批准号: 16580261
• 负责人: SATO Reeko
• 金额: $ 2.43万
• 依托单位: Iwate University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2004
• 资助国家: 日本
• 起止时间: 2004 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16580261/
• 关键词: lactoferrin; feline immunodeficiency virus (FIV); immunodeficiency; chronic inflammation; cat; lymphocyte proliferation; interferon-γ; cytokine; PBMC; IFN-γ

1)The effects of orally-administered bovine lactoferrin (bLF) on lymphocyte functions in FIV-infected catsThe effects of bLF on ConA-induced proliferation of peripheral lymphocyte in healthy and FIV-infected cats were investigated. Orally-administered bLF showed the inhibition of lymphocyte proliferation both in healthy and FIV- infected cats. Co-incubation of bLF and peripheral lymphocytes also showed the inhibition of lymphocyte proliferation both in healthy and FIV-infected cats.2)The effects of bLF and ConA on cytokine mRNA expression in feline peripheral lymphocyteAfter the co-incubation of ConA and peripheral lymphocyte, mRNA expression of IFN-γ,IL-1β,TNF-α and IL-12p40 was investigated by RT-PCR method. The strong mRNA-expression of IFN-γ was first detected at 4hr after the addition of ConA, however the addition of ConA did not bring the mRNA-expression of other cytokines such as IL-1(3,TNF-α and IL-12p40. After that, the mRNA-expression of IFN-γ was investigated by quantitative … More analysis with real time PCR in order to confirm the result of RT-PCR. We established the method of real time PCR for feline IFN-γ. After the stimulation of ConA, the strong mRNA-expression of IFN-γ was observed in peripheral lymphocyte both of healthy and FIV-infected cats, using real time PCR method. Before ConA stimulation and 10, 20 and 40 min after ConA stimulation, bLF was added to peripheral lymphocyte and ConA-induced mRNA- expression of IFN-γ was determined by real time PCR. Bovine LF inhibited the ConA-induced mRNA-expression of IFN-γ in felime lymphocyte. The inhibition of IFN-γ-mRNA-expression was observed not only when lymphocyte was treated with bLF 30 min before but also 10,20 or 40 min after ConA stimulation.3)The effects of Con A stimulation on the lymphocyte signaling pathways of IFN-γ-mRNA-expressionThe relation of ConA stimulation and signaling pathways of lymphocyte was investigated. Our results suggested that PTK-and ERK-dependent signaling pathways are involved in the ConA-induced expression of IFN-γ-mRNA. Therefore, it is likely that bLF inhibits IFN-γ production by interfering with this signaling pathway.Judging from these results, the beneficial effects of bLF in vivo may be explained by modulatory ability of bLF against feline lymphocyte. These modulatory actions of bLF seemed to be involved in anti-inflammatory effects on the cats with chronic inflammation. Less

1)本研究观察了口服牛乳铁蛋白（bLF）对FIV感染猫外周血淋巴细胞功能的影响。经口给予bLF显示在健康和FIV感染的猫中均抑制淋巴细胞增殖。bLF和ConA对猫外周血淋巴细胞中细胞因子mRNA表达的影响将ConA与猫外周血淋巴细胞共孵育后，采用RT-PCR方法检测IFN-γ、IL-1β、TNF-α和IL-12 p40的mRNA表达。在加入ConA后4小时首次检测到IFN-γ的强mRNA表达，然而，加入ConA并不引起其它细胞因子如IL-1 β、TNF-α和IL-12 p40的mRNA表达。然后，通过定量方法研究IFN-γ的mRNA表达 ...更多信息 用真实的时间PCR进行分析，以证实RT-PCR的结果。建立了猫IFN-γ的真实的实时荧光PCR方法。用真实的时间PCR方法检测到，在ConA刺激后，健康猫和感染FIV猫的外周血淋巴细胞中均能表达IFN-γ mRNA。在ConA刺激前及刺激后10、20和40 min，将bLF加入外周血淋巴细胞中，用真实的时间PCR检测ConA诱导的IFN-γ mRNA表达。牛LF抑制ConA诱导的猫淋巴细胞IFN-γ mRNA的表达。在ConA刺激前30 min及刺激后10、20、40 min，bLF均能抑制淋巴细胞IFN-γ-mRNA的表达。3）ConA刺激对淋巴细胞IFN-γ-mRNA表达信号通路的影响结果提示，在ConA诱导的IFN-γ-mRNA表达过程中，存在着ERK和ERK依赖的信号通路。因此，bLF可能是通过干扰这一信号通路来抑制IFN-γ的产生，其体内的有益作用可能是通过其对猫淋巴细胞的调节作用来解释的。bLF的这些调节作用似乎参与了对慢性炎症猫的抗炎作用。少

项目成果

Safety of reduced-dosage ketoprofen for long-term oral administrationin healthy dogs.

减少剂量的酮洛芬对健康犬长期口服给药的安全性。

• 发表时间: 2006
• 期刊: Am. J. Vet. Res. (in press)
• 作者: Narita;T.;Sato;R.;Tomizawa;N.;Komori;S.;Tani;K.;Hara;S.
• 通讯作者: S.

Reduction of concanavalin A-induced expression of interferon-y by bovine lactoferrin in feline peripheral blood mononuclear cells.

牛乳铁蛋白在猫外周血单核细胞中减少伴刀豆球蛋白 A 诱导的干扰素-γ 表达。

• 发表时间: 2005
• 期刊: Veterinary Immunology Immunopathology 105
• 作者: Saori Kobayashi;et al.
• 通讯作者: et al.

Modulatory effects of oral administration of enteric-coated lactoferrin on neutrophil functions in feline immunodeficiency virus(FIV) infected cats.

口服肠溶乳铁蛋白对猫免疫缺陷病毒（FIV）感染猫中性粒细胞功能的调节作用。

• 发表时间: 2005
• 期刊: International Conference on Lactoferrin : Structure, Function and Applications 7
• 作者: Sato;R.
• 通讯作者: R.

The clinical application of bovine lactoferrin as a immuno-modulator.

牛乳铁蛋白作为免疫调节剂的临床应用。

• 发表时间: 2004
• 期刊: Tama Rinshou Kenkyukai Journal 194
• 作者: Ando T;Kamimura S;et al.;Reeko Sato
• 通讯作者: Reeko Sato

Clinical application of bovine lactoferrin in small animal practice.

牛乳铁蛋白在小动物实践中的临床应用。

• 发表时间: 2004
• 期刊: Miyagi Veterinarian 58
• 作者: Ishiguro K;Baba E;Torii R;Tamada H;Kawate N;Hatoya S;Wijewardana V;Kumagai D;Sugiura K;Sawada T;Inaba T;Reeko Sato
• 通讯作者: Reeko Sato