Interferon-γ induces immunoproteasomes and the presentation of MHC I-associated peptides on human salivary gland cells.
Interferon-γ induces immunoproteasomes and the presentation of MHC I-associated peptides on human salivary gland cells.
复制标题
DOI：
10.1371/journal.pone.0102878
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Hu S
中科院分区：
文献类型：
--
作者：
Arellano-Garcia ME;Misuno K;Tran SD;Hu S
干燥综合征（一种自身免疫性疾病）的一个显着组织病理学特征是唾液腺和泪腺中存在淋巴细胞浸润。这种浸润由活化的淋巴细胞和巨噬细胞组成，已知会产生多种细胞因子，包括干扰素-γ (IFN-γ)。在这项研究中，我们证明IFN-γ强烈诱导人唾液腺（HSG）细胞中免疫蛋白酶体β亚基（β1i、β2i和β5i）的表达和免疫蛋白酶体活性，但相反抑制蛋白酶体β亚基（β1、β2和β5）的表达。质谱分析揭示了 HSG 细胞上潜在的 MHC I 相关肽，包括由于 IFN-γ 刺激而衍生自唾液淀粉酶的胰蛋白酶肽。这些结果表明 IFN-γ 诱导 HSG 细胞中的免疫蛋白酶体，导致 MHC I 相关肽在细胞表面的表达增强。这些呈递肽的唾液腺细胞可以被自身反应性T淋巴细胞识别和靶向。我们还发现，lactacystin是一种蛋白酶体抑制剂，可抑制HSG细胞中β1亚基的表达，并阻断IFN-γ诱导的β1i表达和免疫蛋白酶体活性。然而，HSG细胞中β2i和β5i的表达不受lactacystin的影响。这些结果可能为乳胞素如何阻断蛋白酶体或免疫蛋白酶体的作用机制提供新的见解。
A prominent histopathological feature of Sjögren's syndrome, an autoimmune disease, is the presence of lymphocytic infiltrates in the salivary and lachrymal glands. Such infiltrates are comprised of activated lymphocytes and macrophages, and known to produce multiple cytokines including interferon-gamma (IFN-γ). In this study, we have demonstrated that IFN-γ strongly induces the expression of immunoproteasome beta subunits (β1i, β2i and β5i) and immunoproteasome activity but conversely inhibits the expression of proteasome beta subunits (β1, β2 and β5) in human salivary gland (HSG) cells. Mass spectrometric analysis has revealed potential MHC I-associated peptides on the HSG cells, including a tryptic peptide derived from salivary amylase, due to IFN-γ stimulation. These results suggest that IFN-γ induces immunoproteasomes in HSG cells, leading to enhanced presentation of MHC I-associated peptides on cell surface. These peptide-presenting salivary gland cells may be recognized and targeted by auto-reactive T lymphocytes. We have also found that lactacystin, a proteasome inhibitor, inhibits the expression of β1 subunit in HSG cells and blocks the IFN-γ-induced expression of β1i and immunoproteasome activity. However, the expression of β2i and β5i in HSG cells is not affected by lactacystin. These results may add new insight into the mechanism regarding how lactacystin blocks the action of proteasomes or immunoproteasomes.
登录
查看更多内容
影响因子：
2.1
作者：
Baturone, R.;Soto, M. J.;Giron-Gonzalez, J. A.
通讯作者：
Giron-Gonzalez, J. A.
DOI：
10.1196/annals.1384.003
发表时间：
2007-01-01
期刊：
ORAL-BASED DIAGNOSTICS
影响因子：
--
作者：
Fox, Philip C.
通讯作者：
Fox, Philip C.
影响因子：
64.8
作者：
Groll, M;Ditzel, L;Huber, R
通讯作者：
Huber, R
影响因子：
4.8
作者：
De, M;Jayarapu, K;Griffin, TA
通讯作者：
Griffin, TA
DOI：
10.1152/ajplung.00103.2006
发表时间：
2007-01-01
影响因子：
4.9
作者：
Das, Aparajita;Boggaram, Vijayakumar
通讯作者：
Boggaram, Vijayakumar