Zhan Kang, Jiang MaoCheng, Gong Xiaoxiao, Zhao GuoQi
Institute of Animal Culture Collection and Application, College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
In Vitro Cell Dev Biol Anim. 2018 Apr;54(4):311-320. doi: 10.1007/s11626-017-0226-2. Epub 2018 Mar 12.
Short-chain fatty acids (SCFAs) produced by microbial fermentation of dietary fibers are utilized by intestinal epithelial cells to provide an energy source for the ruminant. Although the regulation of mRNA expression and inflammatory response involved in SCFAs is established in other animals and tissues, the underlying mechanisms of the inflammatory response by SCFAs in goat jejunum epithelial cells (GJECs) have not been understood. Therefore, the objective of the study is to investigate the underlying mechanisms of the effects of SCFAs on SCFA transporters and inflammatory response in GJECs. These results showed that the acetate, butyrate, and SCFA concentration were markedly reduced in GJECs (p < 0.01). In addition, the propionate concentration was significantly decreased in GJECs (p < 0.05). The mRNA abundance of monocarboxylate transporter 1 (MCT1), MCT4, NHE1, and putative anion transporter 1 (PAT1) was elevated (p < 0.05) by 20 mM SCFAs at pH 7.4 compared with exposure to the pH group. The anion exchanger 2 (AE2) was increased (p < 0.05) by 20 mM SCFAs at pH 6.2. The mRNA abundance of vH ATPase B subunit (vH ATPase) was attenuated by SCFAs. For inflammatory responses, IL-1β and TNF-α were increased with SCFAs (p < 0.05). In addition, IκBα involved in NF-κB signaling pathways was disrupted by SCFAs. Consistently, p-p65 signaling molecule was enhanced by adding SCFAs. However, IL-6 was attenuated by adding SCFAs (p < 0.05). Furthermore, p-ErK1/2 mitogen-activated protein kinase (MAPK) signaling pathway was downregulated by adding SCFAs. In conclusion, these novel findings demonstrated that mRNA abundance involved in SCFA absorption is probably associated to SCFAs and pH value, and mechanism of the inflammatory response by SCFAs may be involved in NF-κB and p-ErK1/2 MAPK signaling pathways in GJECs. These pathways may mediate protective inflammation response in GJECs.
膳食纤维经微生物发酵产生的短链脂肪酸（SCFAs）被肠道上皮细胞利用，为反刍动物提供能量来源。虽然SCFAs参与的mRNA表达调控和炎症反应在其他动物和组织中已有研究，但SCFAs在山羊空肠上皮细胞（GJECs）中引发炎症反应的潜在机制尚不清楚。因此，本研究的目的是探究SCFAs对GJECs中SCFA转运体及炎症反应影响的潜在机制。这些结果表明，GJECs中的乙酸盐、丁酸盐和SCFA浓度显著降低（p < 0.01）。此外，GJECs中的丙酸盐浓度显著下降（p < 0.05）。与pH对照组相比，在pH 7.4条件下，20 mM SCFAs使单羧酸转运体1（MCT1）、MCT4、钠氢交换体1（NHE1）和推定阴离子转运体1（PAT1）的mRNA丰度升高（p < 0.05）。在pH 6.2条件下，20 mM SCFAs使阴离子交换蛋白2（AE2）增加（p < 0.05）。SCFAs使空泡型H⁺-ATP酶B亚基（vH ATPase）的mRNA丰度降低。对于炎症反应，SCFAs使白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）增加（p < 0.05）。此外，参与核因子κB（NF-κB）信号通路的IκBα被SCFAs破坏。一致地，添加SCFAs增强了磷酸化p65信号分子。然而，添加SCFAs使白细胞介素-6（IL-6）减弱（p < 0.05）。此外，添加SCFAs使磷酸化细胞外信号调节激酶1/2（p-ErK1/2）丝裂原活化蛋白激酶（MAPK）信号通路下调。总之，这些新发现表明，参与SCFA吸收的mRNA丰度可能与SCFAs和pH值有关，SCFAs引发炎症反应的机制可能涉及GJECs中的NF-κB和p-ErK1/2 MAPK信号通路。这些通路可能介导GJECs中的保护性炎症反应。
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