title: Membrane translocation of IL-33 receptor in ventilator induced lung injury.
abstract: Ventilator-induced lung injury is associated with inflammatory mechanism and causes high mortality. The objective of this study was to discover the role of IL-33 and its ST2 receptor in acute lung injury induced by mechanical ventilator (ventilator-induced lung injury; VILI). Male Wistar rats were intubated after tracheostomy and received ventilation at 10 cm H2O of inspiratory pressure (PC10) by a G5 ventilator for 4 hours. The hemodynamic and respiratory parameters were collected and analyzed. The morphological changes of lung injury were also assessed by histological H&E stain. The dynamic changes of lung injury markers such as TNF-α and IL-1β were measured in serum, bronchoalveolar lavage fluid (BALF), and lung tissue homogenization by ELISA assay. During VILI, the IL-33 profile change was detected in BALF, peripheral serum, and lung tissue by ELISA analysis. The Il-33 and ST2 expression were analyzed by immunohistochemistry staining and western blot analysis. The consequence of VILI by H&E stain showed inducing lung congestion and increasing the expression of pro-inflammatory cytokines such as TNF-α and IL-1β in the lung tissue homogenization, serum, and BALF, respectively. In addition, rats with VILI also exhibited high expression of IL-33 in lung tissues. Interestingly, the data showed that ST2L (membrane form) was highly accumulated in the membrane fraction of lung tissue in the PC10 group, but the ST2L in cytosol was dramatically decreased in the PC10 group. Conversely, the sST2 (soluble form) was slightly decreased both in the membrane and cytosol fractions in the PC10 group compared to the control group. In conclusion, these results demonstrated that ST2L translocation from the cytosol to the cell membranes of lung tissue and the down-expression of sST2 in both fractions can function as new biomarkers of VILI. Moreover, IL-33/ST2 signaling activated by mechanically responsive lung injury may potentially serve as a new therapy target.
authors: Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan; P.h.D Program in Nutrition and Food Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Shih-Hsing
authors: SH
authors: Yang
authors: Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Jau-Chen
authors: JC
authors: Lin
authors: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
authors: Shu-Yu
authors: SY
authors: Wu
authors: Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan.
authors: Kun-Lun
authors: KL
authors: Huang
authors: Department of Respiratory Therapy, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Fang
authors: F
authors: Jung
authors: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Ming-Chieh
authors: MC
authors: Ma
authors: P.h.D Program in Nutrition and Food Science, Fu Jen Catholic University, New Taipei City, Taiwan; Department of Nutritional Science, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Guoo-Shyng
authors: GS
authors: Wang Hsu
authors: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Guey-Mei
authors: GM
authors: Jow
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002462:Cell Membrane / Q000235:genetics; D003600:Cytosol; D005786:Gene Expression Regulation; D006801:Humans; D000067596:Interleukin-33 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D021381:Protein Transport / Q000235:genetics; D051381:Rats; D017472:Receptors, Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D014139:Tracheostomy; D055397:Ventilator-Induced Lung Injury / Q000235:genetics* / Q000503:physiopathology; D012122:Ventilators, Mechanical / Q000009:adverse effects
chemical_list: C553108:Il33 protein, rat; D000067596:Interleukin-33; D017472:Receptors, Interleukin-1; C000589812:ST2 protein, rat