Tumor necrosis factor expression is ameliorated after exposure to an acidic environment.
Tumor necrosis factor expression is ameliorated after exposure to an acidic environment.
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DOI：
10.1016/j.jss.2010.08.005
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发表时间：
2012-03
期刊：
影响因子：
--
通讯作者：
De Maio A
中科院分区：
文献类型：
--
作者：
Grabowski J;Vazquez DE;Costantini T;Cauvi DM;Charles W;Bickler S;Talamini MA;Vega VL;Coimbra R;De Maio A
众所周知，腹腔镜手术具有多种临床益处，包括减轻疼痛和缩短住院时间。这些作用与炎症反应的减少有关。先前的研究表明，腹腔镜手术后炎症减少是二氧化碳吹入的产物，这降低了腹膜pH值。本研究的目的是调查细胞和分子机制，负责暴露于酸性环境后反应降低。将鼠巨噬细胞系（J744）在pH 6.0或pH 7.4的培养基中在37°C下孵育3小时。然后，在pH 7.4下用脂多糖（LPS）刺激细胞，测量TNF-α的表达（qRT-PCR或ELISA）和细胞内pH。同时检测CD 14、Toll样受体4的表达及NF-κB核转位。与中性pH条件下的细胞相比，在pH 6.0下预孵育的细胞中观察到LPS诱导的TNF-α表达水平显著降低。TNF-α水平的降低与CD 14和Toll样受体4的细胞表面表达降低无关。暴露于细胞外酸性环境导致IκB磷酸化和NF-κB核转位减少，继发于胞浆pH值的显著下降。这些观察结果为暴露于低细胞外pH值后TNF-α表达减少提供了潜在机制，这可能与腹腔镜手术期间CO2吹入后的酸化有关。此外，细胞外酸性pH环境可能成为巨噬细胞功能的重要调节因子。
It has been well established that laparoscopic surgery presents several clinical benefits, including reduced pain and a shorter hospital stay. These effects have been associated with a decrease in the inflammatory response. Previous studies have demonstrated that reduced inflammation after laparoscopic surgery is the product of carbon dioxide insufflation, which decreases peritoneal pH. The objective of this study was to investigate the cellular and molecular mechanisms responsible for the reduced response after exposure to acidic environments. A murine macrophage line (J744) was incubated in culture medium at pH 6.0 or pH 7.4 for 3 hours at 37°C. Then, cells were stimulated with lipopolysaccharide (LPS) at pH 7.4, the expression of TNF-α (qRT-PCR or ELISA) and intracellular pH were measured. In addition, CD14 and Toll-like receptor 4 expression and and NF-κB nuclear translocation were analyzed. A significant decrease in LPS-induced TNF-α expression levels was observed in cells pre-incubated at pH 6.0 in comparison with cells at neutral pH conditions. This decrease in TNF-α levels was not associated with a reduction in cell surface expression of CD14 and Toll-like receptor 4. Exposure to an extracellular acidic environment resulted in a reduction of IκB phosphorylation and NF-κB nuclear translocation, secondary to a significant drop in cytosolic pH. These observations provide a potential mechanism for the reduced expression of TNF-α after exposure to low extracellular pH, which may be related to acidification after CO2 insufflation during laparoscopic surgery. In addition, extracellular acidic pH environments could emerge as an important regulator of macrophage function.
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影响因子：
9
作者：
Hanly, EJ;Mendoza-Sagaon, M;Talamini, MA
通讯作者：
Talamini, MA
影响因子：
2.9
作者：
THOMAS, JA;BUCHSBAUM, RN;RACKER, E
通讯作者：
RACKER, E
DOI：
10.1007/s00464-001-0063-x
发表时间：
2002-03-01
影响因子：
3.1
作者：
Sietses, C;von Blomberg, ME;Cuesta, MA
通讯作者：
Cuesta, MA
DOI：
10.1007/s00464-004-2175-6
发表时间：
2006-04-01
影响因子：
3.1
作者：
Kos, M;Kuebler, JF;Ure, BM
通讯作者：
Ure, BM
影响因子：
9
作者：
West, MA;Hackam, DJ;Rotstein, OD
通讯作者：
Rotstein, OD