Inflammatory caspases are critical for enhanced cell death in the target tissue of Sjögren's syndrome before disease onset.
Inflammatory caspases are critical for enhanced cell death in the target tissue of Sjögren's syndrome before disease onset.
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DOI：
10.1038/icb.2008.70
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发表时间：
2009-01
影响因子：
4
通讯作者：
Cha, Seunghee
中科院分区：
文献类型：
--
作者：
Bulosan, Marievic;Pauley, Kaleb M.;Yo, Kyumee;Chan, Edward K. L.;Katz, Joseph;Peck, Ammon B.;Cha, Seunghee
迄今为止，很少有人知道为什么外分泌腺受到免疫细胞浸润的干燥综合征（SjS）。用SjS-prone-C57 BL/6. NOD-Aec 1Aec 2小鼠进行的研究显示，在疾病发作前8周，下颌下腺（SMX）的腺体稳态发生改变，并提示可能涉及炎性半胱天冬酶（半胱天冬酶-11和-1）。为了确定炎症性半胱天冬酶是否是SJS样疾病前上皮细胞死亡增加的关键，我们研究了涉及半胱天冬酶-11/半胱天冬酶-1轴的分子事件。我们的研究结果显示，在8周时，C57 BL/6. NOD-Aec 1Aec 2的SMX中，巨噬细胞中的caspase-11、STAT-1活性、caspase-1活性和凋亡上皮细胞同时上调。Caspase-1是IL-1β和IL-18分泌的关键因子，导致唾液中IL-18水平升高。有趣的是，TUNEL阳性细胞在C57 BL/6. NOD-Aec 1Aec 2的SMX中不与caspase-11共定位，表明caspase-11以非细胞自主的方式起作用。只有在LPS和IFN-γ刺激的人单核细胞THP-1细胞存在时，人唾液腺（HSG）细胞系的凋亡增加才发生，当THP-1细胞中的caspase-1被siRNA靶向时，这种凋亡被逆转。总之，我们的研究发现，炎症性半胱氨酸蛋白酶在促进促炎微环境和影响SjS发病前靶组织中上皮细胞死亡增加方面至关重要。
To date, little is known why exocrine glands are subject to immune cell infiltrations in Sjögren’s syndrome (SjS). Studies with SjS-prone-C57BL/6.NOD-Aec1Aec2 mice showed altered glandular homeostasis in the submandibular glands (SMX) at 8 weeks prior to disease onset and suggested potential involvement of inflammatory caspases (caspases-11 and -1). To determine if inflammatory caspases are critical for the increased epithelial cell death prior to SjS-like disease, we investigated molecular events involving caspase-11/caspase-1 axis. Our results revealed concurrent up-regulation of caspase-11 in macrophages, STAT-1 activity, caspase-1 activity, and apoptotic epithelial cells in the SMX of C57BL/6.NOD-Aec1Aec2 at 8 weeks. Caspase-1, a critical factor for IL-1β and IL-18 secretion, resulted in elevated level of IL-18 in saliva. Interestingly, TUNEL-positive cells in the SMX of C57BL/6.NOD-Aec1Aec2 were not co-localized with caspase-11, indicating that caspase-11 functions in a non-cell autonomous manner. Increased apoptosis of a human salivary gland (HSG) cell line occurred only in the presence of LPS-and IFN-γ-stimulated human monocytic THP-1 cells, which was reversed when caspase-1 in THP-1 cells was targeted by siRNA. Taken together, our study discovered that inflammatory caspases are essential in promoting pro-inflammatory microenvironment and influencing increased epithelial cell death in the target tissues of SjS before disease onset.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
--
作者：
Griffith, KJ;Chan, EKL;Fritzler, MJ
通讯作者：
Fritzler, MJ
DOI：
10.1016/s0300-9785(82)80006-9
发表时间：
1982-01-01
期刊：
INTERNATIONAL JOURNAL OF ORAL SURGERY
影响因子：
--
作者：
SATO, M;YOSHIDA, H;URATA, M
通讯作者：
URATA, M
影响因子：
4.4
作者：
Maxwell, Joseph R.;Yadav, Rajwardhan;Vella, Anthony T.
通讯作者：
Vella, Anthony T.