Role of glutamine in the mediation of E-cadherin, p120-catenin and inflammation in ventilator-induced lung injury

• Published in: Chinese medical journal Vol. 131; no. 7; pp. 804 - 812
• Main Authors: Qiu, Jian-Lei, Song, Bai-Ling, Wang, Yu-Juan, Zhang, Fu-Tao, Wang, Yue-Lan
• Format: Journal Article
• Language: English
• Published: China Wolters Kluwer India Pvt. Ltd 05-04-2018; Medknow Publications and Media Pvt. Ltd; Lippincott Williams & Wilkins Ovid Technologies; Department of Anesthesiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, China; Department of Anesthesiology, Dezhou People's Hospital, Dezhou, Shandong 253014, China%Department of Surgery, Rizhao People's Hospital, Rizhao, Shandong 276826, China%Department of Anesthesiology, Rizhao People's Hospital, Rizhao, Shandong 276826, China%Department of Emergency, Dezhou People's Hospital, Dezhou, Shandong 253014, China%Department of Anesthesiology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shandong 250014, China; Medknow Publications & Media Pvt Ltd; Wolters Kluwer
• Subjects: Adherens Junctions; Glutamine; Inflammatory Cytokines; Ventilation-induced Lung Injury; Analysis; Animals; Cadherins; Cadherins - metabolism; Catenins - metabolism; Cell adhesion & migration; Cytokines; Edema; Experiments; Glutamine; Glutamine - metabolism; Inflammation; Inflammation - metabolism; Interleukin-6 - metabolism; Laboratory animals; Lung - metabolism; Lung - pathology; Lung diseases; Lungs; Mice; Mice, Inbred C57BL; Original; Permeability; Studies; Tumor necrosis factor-TNF; Ventilator-Induced Lung Injury - immunology; Ventilator-Induced Lung Injury - metabolism; Ventilators; United States > US; China; Adherens Junctions; Inflammatory Cytokines; Ventilation-induced Lung Injury; Glutamine
• ISSN: 0366-6999; 2542-5641
• DOI: 10.4103/0366-6999.228230

Background: Ventilator-induced lung injury (VILI) is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated. This study examined the relationship between inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-10) and adherens junctions (E-cadherin, p120-catenin), which were ameliorated by glutamine in VILI, both in vitro and in vivo.
Methods: For the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table (n = 6 in each group): control (Group C); low tidal volume (Group L); low tidal volume + glutamine (Group L + G); high tidal volume (Group H); and high tidal volume + glutamine (Group H + G). Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 (MLE-12) cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence.
Results: In vivo, compared with Group C, total cell counts (t = −28.182, P < 0.01), the percentage of neutrophils (t = −28.095, P < 0.01), IL-6 (t = −28.296, P < 0.01), and TNF-α (t = −19.812, P < 0.01) in bronchoalveolar lavage (BAL) fluid, lung injury scores (t = −6.708, P < 0.01), and the wet-to-dry ratio (t = −15.595, P < 0.01) were increased in Group H; IL-10 in BAL fluid (t = 9.093, P < 0.01) and the expression of E-cadherin (t = 10.044, P < 0.01) and p120-catenin (t = 13.218, P < 0.01) were decreased in Group H. Compared with Group H, total cell counts (t = 14.844, P < 0.01), the percentage of neutrophils (t = 18.077, P < 0.01), IL-6 (t = 18.007, P < 0.01), and TNF-α (t = 10.171, P < 0.01) in BAL fluid were decreased in Group H + G; IL-10 in BAL fluid (t = −7.531, P < 0.01) and the expression of E-cadherin (t = −14.814, P < 0.01) and p120-catenin (t = −9.114, P < 0.01) were increased in Group H + G. In vitro, compared with the nonstretching group, the levels of IL-6 (t = −21.111, P < 0.01) and TNF-α (t = −15.270, P < 0.01) were increased in the 20% cyclic stretching group; the levels of IL-10 (t = 5.450, P < 0.01) and the expression of E-cadherin (t = 17.736, P < 0.01) and p120-catenin (t = 16.136, P < 0.01) were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 (t = 11.818, P < 0.01) and TNF-α (t = 8.631, P < 0.01) decreased in the glutamine group; the levels of IL-10 (t = −3.203, P < 0.05) and the expression of E-cadherin (t = −13.567, P < 0.01) and p120-catenin (t = −10.013, P < 0.01) were increased in the glutamine group.
Conclusions: High tidal volume mechanical ventilation and 20% cyclic stretching could cause VILI. Glutamine regulates VILI by improving cytokines and increasing the adherens junctions, protein E-cadherin and p120-catenin, to enhance the epithelial barrier function.