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Inflammation

, Volume 42, Issue 2, pp 426–439 | Cite as

Autophagy Activation Improves Lung Injury and Inflammation in Sepsis

  • Hongying ZhaoEmail author
  • Hongguang Chen
  • Meng Xiaoyin
  • Guotao Yang
  • Ying Hu
  • Keliang Xie
  • Yonghao Yu
ORIGINAL ARTICLE
  • 298 Downloads

Abstract

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) undergoes the process of pathological event including lung tissue dysfunction, pulmonary edema, and inflammation in sepsis. Autophagy is a cytoprotective process recognized as one of the major pathways for degradation and recycling of cellular constituents. Autophagy as a protective or maladaptive response was still confused in ALI during sepsis. Acute lung injury was performed by cecal ligation and puncture (CLP). Autophagic inducer rapacymin and inhibitor 3-MA and autophagosomal-lysosome fusion inhibitor bafilomucin (Baf) A1 and chloroquine (CQ) were administrated by intraperitoneal injection at 1 h after CLP operation. Microtubule-associated protein light chain 3 II (LC3II), Beclin 1, Rab7, and lysosome-associated membrane protein type 2 (LAMP2) were detected by western blotting. Seven-day survival rate of septic mice was observed. Histologic scores, lung wet-to-dry (W/D) weight ratio, oxygenation index (PaO2/FiO2), total cells and polymorphonuclear neutrophils (PMN) in bronchial alveolar lavage fluid (BALF) and myeloperoxidase (MPO) activity and cytokine tumor necrosis factor (TNF)-α, high-mobility group box (HMGB)1, interleukin (IL)-6, IL-10, and monocyte chemotactic protein (MCP)1 were measured after sham or ALI operation. ALI induced the increasing expression of autophagy-related protein LC3II, Beclin 1, Rab7, and LAMP2 in CLP operation. Autophagic inducer rapacymin significantly induced the expression of LC3II, Beclin 1, LAMP2, and Rab7 in mice model of CLP, and inhibitor 3-MA reduced expression of LC3II, Beclin 1, LAMP2, and Rab7 expressions in CLP + RAP mice compared to CLP group. Compared with ALI group, Baf and CQ obviously elevated the level of LC3II and Beclin 1, and reduced the LAMP2 and Rab7 expressions in CLP + Baf group and ALI + CQ group. Compared with CLP group, autophagic inducer rapacymin improved the survival rate, histologic scores, lung wet/dry weight ratio, PaO2/FiO2, total cells, and PMNS in BALF and MPO activity and cytokines TNF-α, HMGB1, IL-6, IL-10, and MCP1 in CLP + RAP group, but there were exacerbated above indicators in CLP + 3-MA group, CLP + Baf group, and CLP + CQ group. Autophagy activation participated in the pathophysiologic process of sepsis, and alleviated the cytokine excessive release and lung injury in sepsis.

KEY WORDS

ALI/ARDA autophagy lung injury inflammation 

Abbreviations

3-MA

3-Methyladenine

ALI/ARDS

Acute lung injury/acute respiratory distress syndrome

Baf

Bafilomucin A1

BALF

Bronchial alveolar lavage fluid

CQ

Chloroquine

ELISA

Enzyme-linked immunosorbent assay

HMGB1

High-mobility group box 1

IL

Interleukin

LAMP2

Lysosome-associated membrane protein type 2

LC3II

Microtubule-associated protein light chain 3 II

LPS

Lipopolysaccharide

MCP

Monocyte chemotactic protein

MPO

Myeloperoxidase

PBS

Phosphate-buffered solution

PMN

Polymorphonuclear

TNF

Tumor necrosis factor

W/D

Wet-to-dry

Notes

Funding

This work was supported by research grants from the National Natural Science Foundation of China (81471842, 81601667, 81671888, 81772043) and the Natural Science Foundation of the Tianjin Science Committee (17JCYBJC24800).

Compliance with Ethical Standards

Conflict of Interest

The authors declare that they have no conflict of interest.

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Hongying Zhao
    • 1
    Email author
  • Hongguang Chen
    • 2
  • Meng Xiaoyin
    • 3
  • Guotao Yang
    • 4
  • Ying Hu
    • 5
  • Keliang Xie
    • 2
  • Yonghao Yu
    • 2
  1. 1.Department of GeriatricCangzhou Central HospitalCangzhou CityPeople’s Republic of China
  2. 2.Department of AnesthesiologyTianjin Medical University General Hospital, Tianjin Research Institute of AnesthesiologyTianjinPeople’s Republic of China
  3. 3.Department of Gynecology and ObstetricsTianjin HospitalTianjinChina
  4. 4.Department of NeurologyCangzhou Central HospitalCangzhou CityPeople’s Republic of China
  5. 5.Department of AnesthesiologyChildren’s Hospital of ZhengzhouZhengzhouPeople’s Republic of China

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