Lack of enteral nutrition blunts extracellular-regulated kinase phosphorylation in gut-associated lymphoid tissue
Lack of enteral nutrition blunts extracellular-regulated kinase phosphorylation in gut-associated lymphoid tissue
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DOI：
10.1097/01.shk.0000239760.13206.18
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发表时间：
2007-03-01
期刊：
影响因子：
3.1
通讯作者：
Mochizuki, Hidetaka
中科院分区：
文献类型：
--
作者：
Maeshirna, Yoshinori;Fukatsu, Kazuhiko;Mochizuki, Hidetaka
信号转导蛋白的丝裂原激活蛋白激酶 (MAPK) 家族（细胞外调节激酶 [ERK]、p38 等）包括重要的细胞内炎症介质，在宿主防御中发挥着关键作用。 ERK 和 p38 的磷酸化负责细胞增殖、细胞分化和细胞死亡。我们假设，在缺乏肠内营养的情况下，肠道相关淋巴组织 (GALT) 功能受损与 GALT 细胞中 MAPK 磷酸化降低有关。 53 只雄性癌症研究所小鼠被随机分为 3 组；随意进食、胃内 (IG)-TPN 和静脉内 (IV)-TPN。 TPN 组给予标准 TPN 溶液。喂养 5 天后，分离来自派伊尔淋巴结 (PP)、固有层 (LP) 细胞和小肠上皮内 (IE) 间隙的淋巴细胞。测定GALT淋巴细胞数量。将淋巴细胞在有或没有 50 ng/mL 佛波醇肉豆蔻酸酯乙酸酯 (PMA) 的情况下孵育 15 分钟，并使用激光扫描细胞术测定磷酸化 ERK (p-ERK) 和 p38 (p-p38) 水平。在所有三组的 PP（GALT 诱导位点）淋巴细胞中，PMA 后 p-ERK 均增加。然而，GALT 效应位点（IE 和 LP）中的 ERK 磷酸化仅在肠内组中增强。在三组中，任何 GALT 位点的 p38 磷酸化均未因 PMA 的反应而增加。在另一组小鼠 (n = 33) 中，使用含或不含 PMA 的 BrdU 评估体外 LP 淋巴细胞增殖。在IG-TPN和chow组中，PMA使细胞增殖增加或维持在高水平，但在IV-TPN组中细胞增殖仍然较低。总之，缺乏肠内喂养会削弱 GALT 效应位点对 PMA 刺激的 ERK 激活和细胞增殖，这可能是 GALT 功能降低的重要机制。营养对 GALT p38 磷酸化的影响必须与其他类型和剂量的兴奋剂一起评估。
The mitogen-activated protein kinase (MAPK) family (extracellular-regulated kinase [ERK], p38, etc.) of signal transduction proteins includes important intracellular mediators of inflammation, playing critical roles in host defense. Phosphorylations of ERK and p38 are responsible for cell proliferation, cell differentiation, and cell death. We hypothesized that impaired gut-associated lymphoid tissue (GALT) function in the absence of enteral nutrition is associated with reduced MAPK phosphorylation in GALT cells. Fifty-three male Institute of Cancer Research mice were randomized into 3 groups; ad libitum chow, intragastric (IG)-TPN, and intravenous (IV)-TPN. TPN groups were administered a standard TPN solution. After 5 days of feeding, lymphocytes from Peyer patches (PPs), the lamina propria (LP) cells, and intraepithelial (IE) spaces in the small intestine were isolated. GALT lymphocyte numbers were determined. The lymphocytes were incubated with or without 50 ng/mL of phorbol myristate acetate (PMA) for 15 min, and phosphorylated ERK (p-ERK) and p38 (p-p38) levels were determined using laser scanning cytometry. In PP (GALT inductive site) lymphocytes, p-ERK was increased after PMA in all three groups. However, ERK phosphorylation in GALT effector sites (IE and LP) was enhanced only in the enteral groups. p38 phosphorylation was not increased in any GALT sites, in any of the three groups, in response to PMA. In another set of mice (n = 33), in vitro LP lymphocyte proliferation was assessed with BrdU with or without PMA. Cell proliferation was increased or maintained at high level with PMA in the IG-TPN and chow group, but remained low in the IV-TPN group. In conclusion, lack of enteral feeding blunts ERK activation and cell proliferation in response to PMA stimulation in GALT effector sites, which may be an important mechanism underlying reduced GALT function. The influence of nutrition on GALT p38 phosphorylation must be assessed with other types and dosages of stimulants.