HMGB1 regulates IL-33 expression in acute respiratory distress syndrome.
The development and progression of acute respiratory distress syndrome (ARDS) has been shown to be regulated by cytokines. IL-33 and HMGB1 are conventionally considered as nuclear proteins and have a proinflammatory role. Studies have confirmed that HMGB1 has a significant role in ARDS, but few studies have provided direct evidence to confirm that IL33 is involved in ARDS. The purpose of our study was to determine whether IL-33 is elevated in ARDS and the relationship between IL-33 and HMGB1 in ARDS. We established a mouse model of LPS-induced lung inflammation/injury. Serum, bronchoalveolar lavage fluid (BALF) and lung tissues were obtained to determine the related indicators. IL-33 levels in both the serum, BALF and lungs were significantly increased at 24h after LPS administration compared to the control group. We also found that HMGB1 and other Th1 cytokine/chemokine levels in serum and BALF were also significantly elevated, but the Th2 cytokine levels in serum and BALF didn't increase. To further study the relationship between IL-33 and HMGB1, mice were pretreated with glycyrrhizin (an inhibitor of HMGB1) prior to LPS administration. We found that the expression of IL-33 and HMGB1 were markedly lower than those in the LPS group and the lung injury was ameliorated. The levels of other Th1 cytokines and chemokines in serum and BALF were also significantly decreased. The results showed that IL-33 is likely a major factor in ARDS, and the release of HMGB1 may be correlated with up-regulation of IL-33 expression.
Department of Emergency, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Juan
J
Fu
Department of Emergency, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Shi-Hui
SH
Lin
Department of Emergency, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Chuan-Jiang
CJ
Wang
Department of Emergency, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Sheng-Yuan
SY
Li
Department of Emergency, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Xuan-Yun
XY
Feng
Department of Emergency, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China.
Qiong
Q
Liu
Department of Emergency, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, PR China. Electronic address: xufang828@126.com.
Fang
F
Xu
D000818:Animals; D004195:Disease Models, Animal; D019695:Glycyrrhizic Acid / Q000008:administration & dosage; D024243:HMGB1 Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006801:Humans; D000067596:Interleukin-33 / Q000276:immunology / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000276:immunology; D008168:Lung / Q000276:immunology* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012128:Respiratory Distress Syndrome / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D015854:Up-Regulation
D024243:HMGB1 Protein; C506535:Il33 protein, mouse; D000067596:Interleukin-33; D008070:Lipopolysaccharides; D019695:Glycyrrhizic Acid
Acute respiratory distress syndrome; Cytokine; High mobility group protein-1; Inflammation; Interleukin-33