Interleukin-10 Attenuates Hypochlorous Acid-Mediated Cytotoxicity to HEI-OC1 Cochlear Cells.
Interleukin-10 Attenuates Hypochlorous Acid-Mediated Cytotoxicity to HEI-OC1 Cochlear Cells.
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DOI：
10.3389/fncel.2017.00314
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发表时间：
2017
影响因子：
5.3
通讯作者：
Moon SK
中科院分区：
文献类型：
--
作者：
Mwangi M;Kil SH;Phak D;Park HY;Lim DJ;Park R;Moon SK
炎症反应在获得性听力损失的病理生理过程中起着至关重要的作用，如耳毒性和中耳炎。在我们早期的研究中，我们发现了耳纤维细胞在耳蜗炎症中的关键作用，以及促炎细胞因子在顺铂耳毒性中的重要作用。我们还证实，耳纤维细胞通过血红素加氧酶1（HMOX 1）信号转导抑制白细胞介素-10（IL-10）引起的单核细胞趋化蛋白1（CCL 2）上调，从而抑制耳蜗炎症。然而，目前尚不清楚IL-10如何影响炎症介导的耳蜗损伤。在这里，我们的目的是确定次氯酸，模型炎症介质如何影响耳蜗细胞的活力和IL-10如何影响次氯酸介导的耳蜗细胞损伤。NaOCl，一种次氯酸的钠盐（HOCl）被发现以剂量依赖的方式诱导HEI-OC 1细胞的细胞毒性。过氧化氢和髓过氧化物酶的组合增强顺铂的细胞毒性，这种协同作用被N-乙酰-L-半胱氨酸和ML-171抑制。大鼠螺旋韧带细胞系（RSL）似乎上调抗氧化反应元件（ARE）的活动暴露于IL-10。RSL细胞上调NRF 2（ARE配体）和NR 0 B2的表达，以响应CoPP（HMOX 1诱导剂），但不响应ZnPP（HMOX 1抑制剂）。发现腺病毒介导的NR 0 B2过表达抑制CCL 2上调。腹腔注射脂多糖（LPS）后1天，小鼠血管纹内出现IL-10阳性细胞。注射后5天，在螺旋韧带、螺旋利姆布斯、螺旋神经节和上嵴区观察到IL-10阳性细胞，但在血管纹中未观察到。IL-10 R1似乎在小鼠Corti器官以及HEI-OC 1细胞中表达。HEI-OC 1细胞上调Bcl-xL的表达响应于IL-10，IL-10显示减弱NaOCl诱导的细胞毒性。此外，HEI-OC 1细胞在暴露于顺铂后上调IL-22 RA，并且NaOCl细胞毒性被IL-22抑制。综上所述，我们的研究结果表明，次氯酸参与耳蜗损伤，IL-10可能通过不仅抑制炎症，而且增强耳蜗细胞活力来减少耳蜗损伤。需要进一步的研究来确定耳蜗内IL-10阳性细胞的免疫学特征，并阐明IL-10耳保护活性的分子机制。
Inflammatory reaction plays a crucial role in the pathophysiology of acquired hearing loss such as ototoxicity and labyrinthitis. In our earlier work, we showed the pivotal role of otic fibrocytes in cochlear inflammation and the critical involvement of proinflammatory cytokines in cisplatin ototoxicity. We also demonstrated that otic fibrocytes inhibit monocyte chemoattractant protein 1 (CCL2) upregulation in response to interleukin-10 (IL-10) via heme oxygenase 1 (HMOX1) signaling, resulting in suppression of cochlear inflammation. However, it is still unclear how IL-10 affects inflammation-mediated cochlear injury. Here we aim to determine how hypochlorous acid, a model inflammation mediator affects cochlear cell viability and how IL-10 affects hypochlorous acid-mediated cochlear cell injury. NaOCl, a sodium salt of hypochlorous acid (HOCl) was found to induce cytotoxicity of HEI-OC1 cells in a dose-dependent manner. Combination of hydrogen peroxide and myeloperoxidase augmented cisplatin cytotoxicity, and this synergism was inhibited by N-Acetyl-L-cysteine and ML-171. The rat spiral ligament cell line (RSL) appeared to upregulate the antioxidant response element (ARE) activities upon exposure to IL-10. RSL cells upregulated the expression of NRF2 (an ARE ligand) and NR0B2 in response to CoPP (a HMOX1 inducer), but not to ZnPP (a HMOX1 inhibitor). Adenovirus-mediated overexpression of NR0B2 was found to suppress CCL2 upregulation. IL-10-positive cells appeared in the mouse stria vascularis 1 day after intraperitoneal injection of lipopolysaccharide (LPS). Five days after injection, IL-10-positive cells were observed in the spiral ligament, spiral limbus, spiral ganglia, and suprastrial area, but not in the stria vascularis. IL-10R1 appeared to be expressed in the mouse organ of Corti as well as HEI-OC1 cells. HEI-OC1 cells upregulated Bcl-xL expression in response to IL-10, and IL-10 was shown to attenuate NaOCl-induced cytotoxicity. In addition, HEI-OC1 cells upregulated IL-22RA upon exposure to cisplatin, and NaOCl cytotoxicity was inhibited by IL-22. Taken together, our findings suggest that hypochlorous acid is involved in cochlear injury and that IL-10 potentially reduces cochlear injury through not only inhibition of inflammation but also enhancement of cochlear cell viability. Further studies are needed to determine immunological characteristics of intracochlear IL-10-positive cells and elucidate molecular mechanisms involved in the otoprotective activity of IL-10.
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DOI：
10.1164/ajrccm.156.3.9608032
发表时间：
1997-09-01
影响因子：
24.7
作者：
Hammerschmidt, S;Wahn, H
通讯作者：
Wahn, H
DOI：
10.1084/jem.20082683
发表时间：
2009-07-06
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Pickert G;Neufert C;Leppkes M;Zheng Y;Wittkopf N;Warntjen M;Lehr HA;Hirth S;Weigmann B;Wirtz S;Ouyang W;Neurath MF;Becker C
通讯作者：
Becker C
影响因子：
19.6
作者：
Deng, JP;Kohda, Y;Star, RA
通讯作者：
Star, RA
影响因子：
2.5
作者：
Lang, HN;Ebihara, Y;Schulte, BA
通讯作者：
Schulte, BA
影响因子：
1.6
作者：
Kalinec, GM;Webster, P;Kalinec, F
通讯作者：
Kalinec, F