Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study.
Inhibiting toll-like receptor 4 signaling ameliorates pulmonary fibrosis during acute lung injury induced by lipopolysaccharide: an experimental study.
复制标题
DOI：
10.1186/1465-9921-10-126
复制
发表时间：
2009-12-18
影响因子：
5.8
通讯作者：
Jiang H
中科院分区：
文献类型：
--
作者：
He Z;Zhu Y;Jiang H
Toll样受体4（TLR 4）在脂多糖（LPS）诱导的体外成纤维细胞活化和胶原分泌中是必需的。然而，其对LPS诱导的急性肺损伤（ALI）过程中肺成纤维细胞活化和纤维化起始的影响尚不清楚。本研究的目的是确定抑制TLR 4对体内LPS诱导的ALI和纤维化的影响。腹腔注射LPS建立小鼠急性肺损伤模型。将TLR 4-小发夹RNA（shRNA）慢病毒静脉内注射到小鼠中以抑制TLR 4表达。采用实时荧光定量PCR和Western-blot方法分别检测mRNA和蛋白水平。采用酶联免疫吸附试验（ELISA）检测支气管肺泡灌洗液（BALF）中Ⅰ型前胶原C末端前肽（PICP）含量，采用货车Gieson胶原染色、羟脯氨酸测定和α平滑肌肌动蛋白（α SMA）免疫组化染色检测纤维化程度。腹腔注射LPS后72 h和28 d检测小鼠肺组织中TLR 4、I型前胶原、α-SMA和p-AKT的过度表达。BALF中PICP的ELISA分析、货车Gieson胶原染色、羟脯氨酸测定和α-SMA免疫组化染色显示纤维化程度增加。静脉注射TLR 4-shRNA慢病毒后，所有这些变化均得到缓解。抑制TLR 4信号通路可减轻LPS诱导的ALI早期肺纤维化。
Toll-like receptor 4 (TLR4) is essential in lipopolysaccharide (LPS)-induced fibroblast activation and collagen secretion in vitro. However, its effects on the process of lung fibroblast activation and fibrosis initiation during LPS induced acute lung injury (ALI) remain unknown. The goal of the present study was to determine the effect of inhibiting TLR4 on LPS-induced ALI and fibrosis in vivo. The ALI model was established by intraperitoneal injection of LPS in mice. TLR4-small hairpin RNA (shRNA) lentivirus was injected intravenously into the mice to inhibit TLR4 expression. mRNA and protein levels were detected by real-time PCR and Western-blot analysis, respectively. The contents of the C-terminal propeptide of type I procollagen (PICP) in bronchoalveolar lavage fluid (BALF) were detected by ELISA, and the degree of fibrosis was detected by van Gieson collagen staining, the hydroxyproline assay, and alpha smooth muscle actin (α-SMA) immunohistochemical staining. Overexpression of TLR4, type I procollagen, alpha-SMA, and p-AKT in murine pulmonary tissue after intraperitoneal injection of LPS at 72 hours and 28 days were detected. Moreover, the degree of fibrosis was shown to increase by ELISA analysis of PICP in BALF, van Gieson collagen staining, the hydroxyproline assay, and α-SMA immunohistochemical staining. All of these changes were alleviated by intravenous infection with TLR4-shRNA lentivirus. Inhibiting TLR4 signaling could ameliorate fibrosis at the early stage of ALI induced by LPS.
登录
查看更多内容
DOI：
10.1164/ajrccm.160.6.9811084
发表时间：
1999-12-01
影响因子：
24.7
作者：
Armstrong, L;Thickett, DR;Millar, AB
通讯作者：
Millar, AB
影响因子：
3.9
作者：
WOESSNER, JF
通讯作者：
WOESSNER, JF
影响因子：
4.4
作者：
Fan, J;Kapus, A;Rotstein, OD
通讯作者：
Rotstein, OD
DOI：
10.1084/jem.20061273
发表时间：
2007-05-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Kang HR;Lee CG;Homer RJ;Elias JA
通讯作者：
Elias JA
影响因子：
3.6
作者：
Chetty, Anne;Cao, Gong-Jee;Nielsen, Heber C.
通讯作者：
Nielsen, Heber C.