title: Preconditioning of physiological cyclic stretch attenuated HMGB1 expression in pathologically mechanical stretch-activated A549 cells and ventilator-induced lung injury rats through inhibition of IL-6/STAT3/SOCS3.
abstract: Previous studies have shown that physiologically cyclic stretch (5% CS) attenuated both oxidative- and LPS-induced increases in HMGB1 expression via STAT3. However, little information exists about the effect of precondition of physiological cyclic stretch (CS) on the expression of HMGB 1, which play a crucial role in ventilator-induced lung injury (VILI). We found that 5% CS-preconditioning significantly inhibited HMGB 1 expression, but not HMGB 1 receptors. 5% CS-preconditioning inhibits the IL-6/STAT3 pathway, and the inhibitory effect on the expression of HMGB 1 induced by 5% CS-preconditioning is abolished by additional treatment of rmIL-6. 5% CS-preconditioning also induces SOCS3 upregulation, and 5% CS-preconditioning fails to inhibit the IL-6/STAT3 pathway in cells transfected with SOCS3 siRNA. Moreover, low tidal volume ventilation preconditioning also decreases the severity of VILI evidenced by the markedly improved pulmonary alveolar-capillary barrier dysfunction, wet/dry weight ratio, and histological analysis. These results suggest that preconditioning of physiological 5% CS can reduce the expression of HMGB 1 induced by pathologically mechanical stretch through IL-6/STAT3 pathway associated with up-regulated SOCS3 expression.
authors.affiliation: Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China.
authors.forename: Xiang-Zhi
authors.initials: XZ
authors.lastname: Fang
authors.affiliation: Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China.
authors.forename: Tian-Feng
authors.initials: TF
authors.lastname: Huang
authors.affiliation: Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China.
authors.forename: Cun-Jin
authors.initials: CJ
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China.
authors.forename: Ya-Li
authors.initials: YL
authors.lastname: Ge
authors.affiliation: Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China.
authors.forename: Shun-Yan
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Clinical Medical School of Yangzhou University (Subei People's Hospital of Jiangsu Province), Yangzhou, Jiangsu Province, PR China. Electronic address: gaoju_003@163.com.
authors.forename: Ju
authors.initials: J
authors.lastname: Gao
mesh_terms: D000818:Animals; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D024243:HMGB1 Protein / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000502:physiology*; D010805:Physical Conditioning, Animal; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D012121:Respiration, Artificial / Q000009:adverse effects; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000235:genetics / Q000378:metabolism*; D013990:Tidal Volume; D055397:Ventilator-Induced Lung Injury / Q000517:prevention & control*
chemical_list: D024243:HMGB1 Protein; D015850:Interleukin-6; D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C491410:Socs3 protein, rat; D000071223:Suppressor of Cytokine Signaling 3 Protein
keywords: IL-6/STAT3; Lung injury; Mechanical ventilation; Preconditioning; SOCS3