PMID- 32504758
OWN - NLM
STAT- MEDLINE
DCOM- 20200831
LR  - 20200831
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 256
DP  - 2020 Sep 1
TI  - TLR2 favors OVA-induced allergic airway inflammation in mice through JNK 
      signaling pathway with activation of autophagy.
PG  - 117896
LID - S0024-3205(20)30646-9 [pii]
LID - 10.1016/j.lfs.2020.117896 [doi]
AB  - AIMS: Numerous studies indicate that toll-like receptor 2 (TLR2) led to divergent 
      effects in asthma. The occurrence of autophagy in asthma pathogenesis is still 
      incompletely understood. Here, we aimed to investigate the role of TLR2 and the 
      underlying mechanisms in allergic airway inflammation and autophagy activation. 
      MAIN METHODS: C57BL/6 and TLR2 knockout (TLR2(-/)(-)) mice were subjected to an 
      ovalbumin (OVA)-immunized allergic airway model, and were treated with SP600125. 
      Differential cell counts in bronchoalveolar lavage fluid were determined by 
      Wright's staining. Histological analysis of airway inflammation was determined by 
      haematoxylin and eosin (H&E) and periodic acid-Schiff (PAS) staining. The levels 
      of OVA-specific immunoglobulin E (IgE), tumor necrosis factor alpha (TNF-alpha) and 
      interleukin 10 (IL-10) were detected by enzyme-linked immunosorbent assay 
      (ELISA). Proteins expression in lung tissues was detected by western blot, 
      expression of TLR2 was further observed by immunofluorescence. Autophagy 
      activation was determined by western blot and transmission electron microscopy 
      (TEM). KEY FINDINGS: TLR2 expression was increased upon OVA challenge, and TLR2 
      deficiency was associated with decreased allergic airway inflammation. Meanwhile, 
      TLR2 deficiency weakened autophagy activation. Moreover, inhibition of c-Jun 
      N-terminal kinase (JNK) by SP600125 also suppressed OVA-induced allergic airway 
      inflammation and autophagy activation. Interestingly, treating TLR2(-/-) mice 
      with SP600125 showed similar OVA-induced allergic airway inflammation and 
      autophagy activation compared to that in vehicle-treated TLR2(-/)(-) mice. 
      SIGNIFICANCE: TLR2 might contribute to the maintenance of allergic airway 
      inflammation through JNK signaling pathway accompanying with autophagy 
      activation. These findings may provide a novel signal target for prevention of 
      allergic airway inflammation.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Fang, Lei
AU  - Fang L
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China.
FAU - Shen, Qiying
AU  - Shen Q
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China; Department of Anesthesiology, The First Affiliated Hospital of 
      Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, China.
FAU - Wu, Huimei
AU  - Wu H
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China.
FAU - He, Fang
AU  - He F
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China; No.1 Department of Respiratory Medicine, Anhui Chest Hospital, 
      Jixi Road 397, Hefei, Anhui 230022, China.
FAU - Ding, Peishan
AU  - Ding P
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China.
FAU - Xu, Ke
AU  - Xu K
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China; The First Affiliated Hospital of USTC, Division of Life Sciences 
      and Medicine, University of Science and Technology of China, Hefei, Anhui 230031, 
      China.
FAU - Yan, Xuebo
AU  - Yan X
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China.
FAU - Wang, Muzi
AU  - Wang M
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China.
FAU - Li, Shuai
AU  - Li S
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China; Intensive Care Unit, The Fourth Affiliated Hospital of Anhui 
      Medical University, Huaihai Avenue 100, Hefei, Anhui 230012, China.
FAU - Liu, Rongyu
AU  - Liu R
AD  - Department of Geriatric Respiratory and Critical Care, Provincial Key Laboratory 
      of Molecular Medicine for Geriatric Disease, Anhui Geriatric Institute, The First 
      Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 
      230022, China. Electronic address: rongyuliu@163.com.
LA  - eng
PT  - Journal Article
DEP - 20200603
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (NF-kappa B)
RN  - 0 (Toll-Like Receptor 2)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Animals
MH  - *Autophagy
MH  - Disease Models, Animal
MH  - Goblet Cells/pathology
MH  - Hypersensitivity/*enzymology/*pathology
MH  - Immunoglobulin E/blood
MH  - Lung/pathology/ultrastructure
MH  - *MAP Kinase Signaling System
MH  - Mice, Inbred C57BL
MH  - NF-kappa B/metabolism
MH  - Ovalbumin/*adverse effects
MH  - Pneumonia/blood/*enzymology/*pathology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Toll-Like Receptor 2/*metabolism
OTO - NOTNLM
OT  - Allergic airway inflammation
OT  - Autophagy
OT  - Toll-like receptor 2
OT  - c-Jun N-terminal kinase
COIS- Declaration of competing interest The authors declare no conflict of interest.
EDAT- 2020/06/07 06:00
MHDA- 2020/09/01 06:00
CRDT- 2020/06/07 06:00
PHST- 2020/02/03 00:00 [received]
PHST- 2020/05/21 00:00 [revised]
PHST- 2020/05/31 00:00 [accepted]
PHST- 2020/06/07 06:00 [pubmed]
PHST- 2020/09/01 06:00 [medline]
PHST- 2020/06/07 06:00 [entrez]
AID - S0024-3205(20)30646-9 [pii]
AID - 10.1016/j.lfs.2020.117896 [doi]
PST - ppublish
SO  - Life Sci. 2020 Sep 1;256:117896. doi: 10.1016/j.lfs.2020.117896. Epub 2020 Jun 3.