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抗风湿性大肠杆菌提取物OM-89诱导T细胞对热休克蛋白60和70产生反应。

Antirheumatic E. coli extract OM-89 induces T cell responses to HSP60 and 70.

作者信息

Wendling U, Bloemendal A, Van Der Zee R, Rutten V P, Van Kooten P J, Farine J C, Van Eden W

机构信息

Institute for Infectious Diseases and Immunology, Utrecht University, The Netherlands.

出版信息

Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):565-8. doi: 10.1016/s0192-0561(97)00084-2.

DOI:10.1016/s0192-0561(97)00084-2
PMID:9637355
Abstract

Oral administration of E. coli extract OM-89 is used in treating RA. It has been shown that immune reactivity to heat-shock proteins (hsp) is involved in immunomodulation of arthritis. We evaluated the postulated presence and immunogenicity of hsp's in OM-89. The effects of OM-89 in experimental arthritis were analyzed. Proliferative T cell responses to bacterial hsp60 and hsp70 were found in rats immunized with OM-89. And conversely, immunization with hsp antigens induced OM-89-specific T cell responses. Hsp70 (DnaK) was found to be a major immunogenic constituent of OM-89. Parenteral immunization with OM-89 reduces resistance to adjuvant arthritis (AA), whereas oral administration protects against AA. Given the arthritis inhibitory effect of oral OM-89 in AA our findings suggest peripheral tolerance induced by hsp-specific regulatory T cells as a mode of action for OM-89 as an arthritis suppressive oral drug.

摘要

口服大肠杆菌提取物OM-89可用于治疗类风湿性关节炎(RA)。研究表明,对热休克蛋白(hsp)的免疫反应性参与了关节炎的免疫调节。我们评估了OM-89中hsp的假定存在情况及其免疫原性。分析了OM-89在实验性关节炎中的作用。在用OM-89免疫的大鼠中发现了对细菌hsp60和hsp70的增殖性T细胞反应。相反,用hsp抗原免疫可诱导OM-89特异性T细胞反应。发现hsp70(DnaK)是OM-89的主要免疫原性成分。经肠胃外免疫OM-89会降低对佐剂性关节炎(AA)的抵抗力,而口服则可预防AA。鉴于口服OM-89对AA具有关节炎抑制作用,我们的研究结果表明,hsp特异性调节性T细胞诱导的外周耐受是OM-89作为一种抑制关节炎的口服药物的作用方式。

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1
Antirheumatic E. coli extract OM-89 induces T cell responses to HSP60 and 70.抗风湿性大肠杆菌提取物OM-89诱导T细胞对热休克蛋白60和70产生反应。
Int J Immunopharmacol. 1997 Sep-Oct;19(9-10):565-8. doi: 10.1016/s0192-0561(97)00084-2.
2
Experimental immunization with anti-rheumatic bacterial extract OM-89 induces T cell responses to heat shock protein (hsp)60 and hsp70; modulation of peripheral immunological tolerance as its possible mode of action in the treatment of rheumatoid arthritis (RA).用抗风湿细菌提取物OM-89进行实验性免疫可诱导T细胞对热休克蛋白(hsp)60和hsp70产生反应;调节外周免疫耐受性作为其治疗类风湿关节炎(RA)的可能作用方式。
Clin Exp Immunol. 1997 Oct;110(1):72-8. doi: 10.1046/j.1365-2249.1997.4841378.x.
3
Oral administration of HSP-containing E. coli extract OM-89 has suppressive effects in autoimmunity. Regulation of autoimmune processes by modulating peripheral immunity towards hsp's?口服含热休克蛋白的大肠杆菌提取物OM-89对自身免疫具有抑制作用。通过调节外周对热休克蛋白的免疫来调控自身免疫过程?
Biotherapy. 1998;10(3):223-7. doi: 10.1007/BF02678300.
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Inhibition of adjuvant-induced arthritis by DNA vaccination with the 70-kd or the 90-kd human heat-shock protein: immune cross-regulation with the 60-kd heat-shock protein.用70kd或90kd人热休克蛋白进行DNA疫苗接种对佐剂诱导性关节炎的抑制作用:与60kd热休克蛋白的免疫交叉调节
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5
Oral dosing of rats with OM-89 results in the appearance of specific OM-89 antibodies of the IgG2a isotype: possible significance in the treatment of rheumatoid arthritis.给大鼠口服OM-89会导致出现IgG2a亚型的特异性OM-89抗体:这在类风湿性关节炎治疗中的潜在意义。
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6
Peptide-induced nasal tolerance for a mycobacterial heat shock protein 60 T cell epitope in rats suppresses both adjuvant arthritis and nonmicrobially induced experimental arthritis.肽诱导大鼠对分枝杆菌热休克蛋白60 T细胞表位产生鼻耐受,可抑制佐剂性关节炎和非微生物诱导的实验性关节炎。
Proc Natl Acad Sci U S A. 1997 Apr 1;94(7):3284-9. doi: 10.1073/pnas.94.7.3284.
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Activation of T cells recognizing self 60-kD heat shock protein can protect against experimental arthritis.识别自身60-kD热休克蛋白的T细胞激活可预防实验性关节炎。
J Exp Med. 1995 Mar 1;181(3):943-52. doi: 10.1084/jem.181.3.943.
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Heat-shock protein T-cell epitopes trigger a spreading regulatory control in a diversified arthritogenic T-cell response.热休克蛋白T细胞表位在多样化的致关节炎性T细胞应答中触发一种扩展性调节控制。
Immunol Rev. 1998 Aug;164:169-74. doi: 10.1111/j.1600-065x.1998.tb01218.x.
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Humoral response against heat shock proteins and other mycobacterial antigens after intravesical treatment with bacille Calmette-Guérin (BCG) in patients with superficial bladder cancer.浅表性膀胱癌患者经卡介苗(BCG)膀胱内治疗后针对热休克蛋白和其他分枝杆菌抗原的体液免疫反应
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T cell reactivity to an epitope of the mycobacterial 65-kDa heat-shock protein (hsp 65) corresponds with arthritis susceptibility in rats and is regulated by hsp 65-specific cellular responses.T细胞对分枝杆菌65-kDa热休克蛋白(hsp 65)表位的反应性与大鼠关节炎易感性相关,并受hsp 65特异性细胞反应调控。
Eur J Immunol. 1991 May;21(5):1289-96. doi: 10.1002/eji.1830210529.

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