Mechanical stress is a pro-inflammatory stimulus in the gut: in vitro, in vivo and ex vivo evidence.
Mechanical stress is a pro-inflammatory stimulus in the gut: in vitro, in vivo and ex vivo evidence.
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DOI：
10.1371/journal.pone.0106242
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Shi XZ
中科院分区：
文献类型：
--
作者：
Lin YM;Li F;Shi XZ
在阻塞性和功能性肠病中发现炎性浸润和促炎介质增加，其中存在管腔扩张。然而，引起低水平炎症的原因尚不清楚。我们检验了管腔扩张相关的机械应力可能诱导肠道平滑肌中特定炎症介质表达的假设。采用Flexercell FX-4000 Tension Plus系统对原代培养的大鼠结肠环形平滑肌细胞（RCCSMCs）施加静态机械拉伸（18%伸长）。在大鼠中，在远端结肠中放置阻塞带，诱导体内机械扩张。在原代培养的RCCSMCs中，我们发现静态牵张在3 h内显著诱导iNOS、IL-6和MCP-1 mRNA的表达，分别为6.0（±1.4）、2.5（±0.5）和2.2（±0.5）倍（n = 6 ± 8，p<0.05）。 然而，TNF-α、IL-1β和IL-8的基因表达不受机械拉伸的显著影响。在结肠梗阻的体内模型中，我们发现在机械扩张的近端段中，iNOS、IL-6和MCP-1的基因表达也以时间依赖性的方式显著增加，但在假手术对照或远端段中没有。拉伸近端肌条的条件培养液显著诱导NF-κB p65的转位和磷酸化，而拉伸远端肌条或对照组的条件培养液则无此作用。这种处理进一步增加了幼稚细胞中炎症介质的mRNA表达。然而，用抗大鼠IL-6的中和抗体处理近端节段的条件培养基显著减弱了NF-κB的活化和炎症介质的基因表达。我们的研究表明，机械应力诱导炎症介质，即iNOS，IL-6和MCP-1在结肠SMC的基因表达。进一步的离体研究表明，机械应力在肠道中起到促炎刺激的作用。
Inflammatory infiltrates and pro-inflammatory mediators are found increased in obstructive and functional bowel disorders, in which lumen distention is present. However, what caused the low level inflammation is not well known. We tested the hypothesis that lumen distention- associated mechanical stress may induce expression of specific inflammatory mediators in gut smooth muscle. Static mechanical stretch (18% elongation) was applied in vitro in primary culture of rat colonic circular smooth muscle cells (RCCSMCs) with a Flexercell FX-4000 Tension Plus System. Mechanical distention in vivo was induced in rats with an obstruction band placed in the distal colon. In the primary culture of RCCSMCs, we found that static stretch significantly induced mRNA expression of iNOS, IL-6, and MCP-1 in 3 hours by 6.0(±1.4), 2.5(±0.5), and 2.2(±0.5) fold (n = 6∼8, p<0.05), respectively. However, gene expression of TNF-α, IL-1β, and IL-8 was not significantly affected by mechanical stretch. In the in vivo model of colon obstruction, we found that gene expression of iNOS, IL-6, and MCP-1 is also significantly increased in a time-dependent manner in the mechanically distended proximal segment, but not in the sham controls or distal segments. The conditioned medium from the muscle strips of the stretched proximal segment, but not the distal segment or control, significantly induced translocation and phosphorylation of NF-κB p65. This treatment further increased mRNA expression of inflammatory mediators in the naïve cells. However, treatment of the conditioned medium from the proximal segment with neutralizing antibody against rat IL-6 significantly attenuated the activation of NF-κB and gene expression of inflammatory mediators. Our studies demonstrate that mechanical stress induces gene expression of inflammatory mediators i.e. iNOS, IL-6, and MCP-1 in colonic SMC. Further ex vivo study showed that mechanical stress functions as a pro-inflammatory stimulus in the gut.
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影响因子：
9.1
作者：
MacDermott, RP
通讯作者：
MacDermott, RP
影响因子：
9.8
作者：
Facco, Monica;Brun, Paola;Zaninotto, Giovanni
通讯作者：
Zaninotto, Giovanni
影响因子：
24.5
作者：
Hughes, Patrick A.;Harrington, Andrea M.;Brierley, Stuart M.
通讯作者：
Brierley, Stuart M.
DOI：
10.1152/ajpgi.00216.2004
发表时间：
2004-12-01
影响因子：
4.5
作者：
Cao, WB;Cheng, L;Harnett, KM
通讯作者：
Harnett, KM
DOI：
10.1046/j.1463-1318.2003.00497.x
发表时间：
2003-07-01
期刊：
Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland
影响因子：
--
作者：
D'Hoore, A;Penninckx, F
通讯作者：
Penninckx, F