Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10.
Resistance to bleomycin-induced lung fibrosis in MMP-8 deficient mice is mediated by interleukin-10.
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DOI：
10.1371/journal.pone.0013242
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发表时间：
2010-10-07
期刊：
影响因子：
3.7
通讯作者：
Albaiceta GM
中科院分区：
文献类型：
--
作者：
García-Prieto E;González-López A;Cabrera S;Astudillo A;Gutiérrez-Fernández A;Fanjul-Fernandez M;Batalla-Solís E;Puente XS;Fueyo A;López-Otín C;Albaiceta GM
基质金属蛋白酶（MMPs）可能在肺内具有促纤维化和抗纤维化作用，这是由于其调节胶原蛋白周转和免疫介质的能力。MMP-8是一种胶原酶，其也切割许多细胞因子和趋化因子。为了评估其在肺纤维化中的相关性，野生型和Mmp 8 −/−小鼠用气管内博莱霉素或盐水处理，并在不同时间点收获肺。检测肺组织中的纤维化、胶原、胶原酶、明胶酶、TGFβ和IL-10。Mmp 8 −/−小鼠比野生型小鼠发生更少的纤维化。这与这些突变动物中肺部炎症细胞、MMP-9和IL-10水平的增加有关。体外实验表明，MMP-8切割鼠和人IL-10，并且来自敲除动物的组织显示IL-10加工减少。此外，在博来霉素和胶原蛋白存在下培养来自这些小鼠的肺成纤维细胞，通过蛋白质印迹法测量IL-10和STAT 3活化（响应于IL-10的下游信号）。在细胞培养中，博来霉素仅在野生型小鼠中增加胶原蛋白合成。来自敲除小鼠的成纤维细胞没有显示胶原合成增加，但未加工的IL-10和STAT 3磷酸化水平增加。IL-10的阻断恢复了这种表型，增加了培养物中的胶原蛋白。根据这些结果，我们得出结论，MMP-8的缺乏通过增加IL-10而具有抗纤维化作用，并提出这种金属蛋白酶可能是体内IL-10代谢的相关调节剂。
Matrix metalloproteinases (MMPs) may have pro and antifibrotic roles within the lungs, due to its ability to modulate collagen turnover and immune mediators. MMP-8 is a collagenase that also cleaves a number of cytokines and chemokines. To evaluate its relevance in lung fibrosis, wildtype and Mmp8−/− mice were treated with either intratracheal bleomycin or saline, and lungs were harvested at different time points. Fibrosis, collagen, collagenases, gelatinases, TGFβ and IL-10 were measured in lung tissue. Mmp8−/− mice developed less fibrosis than their wildtype counterparts. This was related to an increase in lung inflammatory cells, MMP-9 and IL-10 levels in these mutant animals. In vitro experiments showed that MMP-8 cleaves murine and human IL-10, and tissue from knockout animals showed decreased IL-10 processing. Additionally, lung fibroblasts from these mice were cultured in the presence of bleomycin and collagen, IL-10 and STAT3 activation (downstream signal in response to IL-10) measured by western blotting. In cell cultures, bleomycin increased collagen synthesis only in wildtype mice. Fibroblasts from knockout mice did not show increased collagen synthesis, but increased levels of unprocessed IL-10 and STAT3 phosphorylation. Blockade of IL-10 reverted this phenotype, increasing collagen in cultures. According to these results, we conclude that the absence of MMP-8 has an antifibrotic effect by increasing IL-10 and propose that this metalloprotease could be a relevant modulator of IL-10 metabolism in vivo.
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影响因子：
4.4
作者：
Gueders, MM;Balbin, M;Cataldo, DD
通讯作者：
Cataldo, DD
DOI：
10.1165/rcmb.2006-0055oc
发表时间：
2006-12-01
影响因子：
6.4
作者：
Garantziotis, Stavros;Brass, David M.;Schwartz, David A.
通讯作者：
Schwartz, David A.
影响因子：
4.8
作者：
Gutierrez-Fernandez, Ana;Inada, Masaki;Puente, Xose S.
通讯作者：
Puente, Xose S.
DOI：
10.4049/jimmunol.0900290
发表时间：
2010-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Quintero PA;Knolle MD;Cala LF;Zhuang Y;Owen CA
通讯作者：
Owen CA
影响因子：
30.8
作者：
Balbín, M;Fueyo, A;López-Otín, C
通讯作者：
López-Otín, C