TLR4 as a negative regulator of keratinocyte proliferation.
TLR4 as a negative regulator of keratinocyte proliferation.
复制标题
DOI：
10.1371/journal.pone.0185668
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Hofbauer GFL
中科院分区：
文献类型：
--
作者：
Iotzova-Weiss G;Freiberger SN;Johansen P;Kamarachev J;Guenova E;Dziunycz PJ;Roux GA;Neu J;Hofbauer GFL
TLR4是一种先天免疫受体，在人皮肤、角质形成细胞和皮肤鳞状细胞癌（SCC）中表达。在本研究中，我们研究了TLR4作为角化细胞增殖的负调节因子的作用。我们发现，TLR4的表达随着培养的角质形成细胞以传代依赖的方式或在富钙条件下的分化而增加。此外，通过特异性敲低TLR4来下调HaCaT角质形成细胞的体外增殖。此外，皮下注射含有shTLR4的HaCaT角质形成细胞在裸鼠体内形成生长肿瘤。相比之下，我们观察到与SCC13 TLR4阴性细胞相比，SCC13稳定过表达TLR4的细胞系在体外增殖降低，迁移增加。在体内，与TLR4阴性肿瘤相比，SCC13 TLR4过表达肿瘤的生长延迟。SCC13肿瘤细胞中TLR4过表达后，ERK1/2和JNK磷酸化，ATF3表达升高。在基因表达阵列中，肿瘤细胞中TLR4的过表达与ATF-3、IL-6、CDH13、CXCL-1和TFPI的基因表达相关。综上所述，TLR4负向调节角质形成细胞的增殖，其过表达可降低SCC细胞的肿瘤生长。
TLR4 is an innate immune receptor with expression in human skin, keratinocytes as well as squamous cell carcinoma (SCC) of the skin. In the present study we investigate the role of TLR4 as a negative regulator of keratinocyte proliferation. We present here that the expression of TLR4 increased with the differentiation of cultured keratinocytes in a passage-dependent manner or under calcium-rich conditions. Moreover, the down-regulation of TLR4 by specific knockdown increased the proliferation of HaCaT keratinocytes in vitro. In addition, subcutaneously injected HaCaT keratinocytes with shTLR4 formed growing tumors in nude mice. In contrast, we observed lower proliferation and increased migration in vitro of the SCC13 cell line stably overexpressing TLR4 in comparison to SCC13 TLR4 negative cells. In vivo, SCC13 TLR4-overexpressing tumors showed delayed growth in comparison to TLR4 negative tumors. The overexpression of TLR4 in SCC13 tumor cells was followed by phosphorylation of ERK1/2 and JNK and increased expression of ATF3. In gene expression arrays, the overexpression of TLR4 in tumor cells correlated with gene expression of ATF-3, IL-6, CDH13, CXCL-1 and TFPI. In summary, TLR4 negatively regulates the proliferation of keratinocytes and its overexpression reduces tumor growth of SCC cells.
登录
查看更多内容
DOI：
10.1590/s0036-46652015000100008
发表时间：
2015-01
影响因子：
1.9
作者：
Oliveira CB;Vasconcellos C;Sakai-Valente NY;Sotto MN;Luiz FG;Belda Júnior W;Sousa Mda G;Benard G;Criado PR
通讯作者：
Criado PR
影响因子：
4
作者：
Ivanov, Vladimir N.;Partridge, Michael A.;Huang, Sarah X. L.;Hei, Tom K.
通讯作者：
Hei, Tom K.
影响因子：
6.5
作者：
Dziunycz, Piotr J.;Lefort, Karine;Hofbauer, Guenther F. L.
通讯作者：
Hofbauer, Guenther F. L.
影响因子：
15.9
作者：
Brooks, Yang Sui;Ostano, Paola;Dotto, G. Paolo
通讯作者：
Dotto, G. Paolo
影响因子：
82.9
作者：
通讯作者：
--