Shao-Kun Liu1,2,3, Li-Bing Ma4,5, Yu Yuan1,2,3, Xiao-Ying Ji6, Wen-Jin Sun1,2,3, Jia-Xi Duan1,2,3, Qing-Ping Zeng1,2,3, Binaya Wasti1,2,3, Bing Xiao1,2,3, Jian-Fei Zheng1,2,3, Ping Chen1,2,3, Xu-Dong Xiang1,2,3. 1. Pulmonary and Critical Care Medicine, The Second Xiangya Hospital, Central South University, Changsha, Hunan 410011, China. 2. Research Unit of Respiratory Disease, Central South University, Changsha, Hunan 410011, China. 3. Diagnosis and Treatment Center of Respiratory Disease, Central South University, Changsha, Hunan 410011, China. 4. Department of Respiratory Medicine, The Affiliated Hospital of Guilin Medical University, Guilin 541001, China. 5. Institute of Respiratory Diseases, Guilin Medical University, Guilin 541001, China. 6. Department of Respiratory Medicine, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen 518106, China.
Abstract
OBJECTIVE: Allergic asthma is a chronic inflammatory disease, which seriously affects the life quality of patients, especially children. Alanylglutamine is a nutritional supplement with potential protective and anti-inflammatory effects, but its function in allergic asthma remains elusive. In this study, we focused on the investigations of the roles and functional mechanism of Alanylglutamine in asthma. METHODS: Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. 16S rDNA sequencing was performed to compare the diversity of intestinal microorganisms under different treatments. Gas chromatography was utilized to screen the intestinal microbe-short-chain fatty acids in the stool. The lung tissue was extracted to determine signaling pathways, including AMPK, NF-κB, mTOR, STAT3, IKKβ, TGF-β, and IL-1β through Western blot or RT-qPCR. RESULTS: It was observed that Alanylglutamine reduced the cytokine in OVA-induced allergic asthma mice. H&E staining showed obvious pneumonia symptoms in the asthma group, while Alanylglutamine alleviated the inflammatory infiltration. Alanylglutamine reversed gut microbiota compositions in OVA-induced allergic asthma mice and enhanced the butyric acid level. The protective role of Alanylglutamine may be associated with the gut microbiota-butyric acid-GPR43 pathway in asthma mice. In contrast to the OVA group, Alanylglutamine activated the protein expression of P-AMPK/AMPK and inhibited the protein expression of P-mTOR/mTOR, P-P65/P65, P-STAT3/STAT3, P-IKKβ/IKKβ, TGF-β, and IL-1β, with similar effects from butyric acid. CONCLUSION: The results indicated that Alanylglutamine might be beneficial for asthma, and its effect was achieved through the regulation on microbiota and the derived metabolites. The therapeutic effects might be associated with AMPK, NF-κB, mTOR, and STAT3 signaling pathways. These findings will help identify effective therapeutic direction to alleviate allergic inflammation of the lungs and airways.
OBJECTIVE: Allergic asthma is a chronic inflammatory disease, which seriously affects the life quality of patients, especially children. Alanylglutamine is a nutritional supplement with potential protective and anti-inflammatory effects, but its function in allergic asthma remains elusive. In this study, we focused on the investigations of the roles and functional mechanism of Alanylglutamine in asthma. METHODS: Ovalbumin (OVA) induction was utilized to establish a mouse asthma model. 16S rDNA sequencing was performed to compare the diversity of intestinal microorganisms under different treatments. Gas chromatography was utilized to screen the intestinal microbe-short-chain fatty acids in the stool. The lung tissue was extracted to determine signaling pathways, including AMPK, NF-κB, mTOR, STAT3, IKKβ, TGF-β, and IL-1β through Western blot or RT-qPCR. RESULTS: It was observed that Alanylglutamine reduced the cytokine in OVA-induced allergic asthma mice. H&E staining showed obvious pneumonia symptoms in the asthma group, while Alanylglutamine alleviated the inflammatory infiltration. Alanylglutamine reversed gut microbiota compositions in OVA-induced allergic asthma mice and enhanced the butyric acid level. The protective role of Alanylglutamine may be associated with the gut microbiota-butyric acid-GPR43 pathway in asthma mice. In contrast to the OVA group, Alanylglutamine activated the protein expression of P-AMPK/AMPK and inhibited the protein expression of P-mTOR/mTOR, P-P65/P65, P-STAT3/STAT3, P-IKKβ/IKKβ, TGF-β, and IL-1β, with similar effects from butyric acid. CONCLUSION: The results indicated that Alanylglutamine might be beneficial for asthma, and its effect was achieved through the regulation on microbiota and the derived metabolites. The therapeutic effects might be associated with AMPK, NF-κB, mTOR, and STAT3 signaling pathways. These findings will help identify effective therapeutic direction to alleviate allergic inflammation of the lungs and airways.
Authors: Gerdien C Melis; Petra G Boelens; Joost R M van der Sijp; Theodora Popovici; Jean-Pascal De Bandt; Luc Cynober; Paul A M van Leeuwen Journal: Br J Nutr Date: 2005-07 Impact factor: 3.718
Authors: Jian Tan; Craig McKenzie; Peter J Vuillermin; Gera Goverse; Carola G Vinuesa; Reina E Mebius; Laurence Macia; Charles R Mackay Journal: Cell Rep Date: 2016-06-21 Impact factor: 9.423