PMID- 37586814
OWN - NLM
STAT- MEDLINE
DCOM- 20231216
LR  - 20240409
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 214
IP  - 3
DP  - 2023 Dec 13
TI  - IL-38 alleviates airway remodeling in chronic asthma via blocking the profibrotic 
      effect of IL-36gamma.
PG  - 260-274
LID - 10.1093/cei/uxad099 [doi]
AB  - Airway remodeling is a major feature of asthma. Interleukin (IL)-36gamma is 
      significantly upregulated and promotes airway hyper-responsiveness (AHR) in 
      asthma, but its role in airway remodeling is unknown. Here, we aimed to 
      investigate the role of IL-36gamma in airway remodeling, and whether IL-38 can 
      alleviate airway remodeling in chronic asthma by blocking the effects of IL-36gamma. 
      IL-36gamma was quantified in mice inhaled with house dust mite (HDM). Extracellular 
      matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36gamma 
      administration to mice. Airway inflammation, AHR, and remodeling were evaluated 
      after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The 
      effects of lung fibroblasts stimulated with IL-36gamma and IL-38 were quantified in 
      vitro. Increased expression of IL-36gamma was detected in lung tissues of HDM-induced 
      asthmatic mice. The intratracheal instillation of IL-36gamma to mice significantly 
      enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts 
      around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a 
      significant alleviation in the airway inflammation, AHR, airway remodeling, and 
      number of activated fibroblasts around airways as compared with the HDM group. In 
      vitro, IL-36gamma promoted the activation and migration of human lung fibroblasts 
      (HFL-1). The administration of IL-38 can counteract these biological processes 
      induced by IL-36gamma in HFL-1cells. The results indicated that IL-38 can mitigate 
      airway remodeling by blocking the profibrotic effects of IL-36gamma in chronic 
      asthma. IL-36gamma may be a new therapeutic target, and IL-38 is a potential 
      candidate agent for inhibiting airway remodeling in asthma.
CI  - (c) The Author(s) 2023. Published by Oxford University Press on behalf of the 
      British Society for Immunology. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Zhang, Min
AU  - Zhang M
AD  - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital 
      of Sun Yat-Sen University, Institute of Respiratory Disease of Sun Yat-Sen 
      University, Guangzhou, Guangdong, China.
FAU - Zhou, Jian-Xia
AU  - Zhou JX
AD  - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital 
      of Sun Yat-Sen University, Institute of Respiratory Disease of Sun Yat-Sen 
      University, Guangzhou, Guangdong, China.
FAU - Huang, Chu-Qin
AU  - Huang CQ
AD  - State Key Laboratory of Respiratory Disease, National Clinical Research Center 
      for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First 
      Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
FAU - Feng, Kang-Ni
AU  - Feng KN
AD  - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital 
      of Sun Yat-Sen University, Institute of Respiratory Disease of Sun Yat-Sen 
      University, Guangzhou, Guangdong, China.
FAU - Zou, Xiao-Ling
AU  - Zou XL
AD  - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital 
      of Sun Yat-Sen University, Institute of Respiratory Disease of Sun Yat-Sen 
      University, Guangzhou, Guangdong, China.
FAU - Cen, Jie-Mei
AU  - Cen JM
AD  - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital 
      of Sun Yat-Sen University, Institute of Respiratory Disease of Sun Yat-Sen 
      University, Guangzhou, Guangdong, China.
FAU - Meng, Ping
AU  - Meng P
AD  - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital 
      of Sun Yat-Sen University, Institute of Respiratory Disease of Sun Yat-Sen 
      University, Guangzhou, Guangdong, China.
FAU - Li, Hong-Tao
AU  - Li HT
AD  - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital 
      of Sun Yat-Sen University, Institute of Respiratory Disease of Sun Yat-Sen 
      University, Guangzhou, Guangdong, China.
FAU - Zhang, Tian-Tuo
AU  - Zhang TT
AUID- ORCID: 0000-0002-9239-0434
AD  - Department of Pulmonary and Critical Care Medicine, The Third Affiliated Hospital 
      of Sun Yat-Sen University, Institute of Respiratory Disease of Sun Yat-Sen 
      University, Guangzhou, Guangdong, China.
LA  - eng
GR  - 81970017/National Natural Science Foundation of China/
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Interleukins)
RN  - 0 (IL-38 protein, human)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Mice
MH  - *Airway Remodeling
MH  - *Asthma/metabolism
MH  - Interleukins/metabolism
MH  - Lung/metabolism
MH  - Inflammation/metabolism
MH  - Disease Models, Animal
MH  - Pyroglyphidae
MH  - Mice, Inbred BALB C
PMC - PMC10719219
OTO - NOTNLM
OT  - airway remodeling
OT  - asthma
OT  - interleukin-36gamma
OT  - interleukin-38
OT  - lung fibroblasts
COIS- None declared.
EDAT- 2023/08/17 00:41
MHDA- 2023/12/17 09:42
PMCR- 2024/08/16
CRDT- 2023/08/16 21:22
PHST- 2023/02/18 00:00 [received]
PHST- 2023/06/30 00:00 [revised]
PHST- 2023/08/11 00:00 [accepted]
PHST- 2024/08/16 00:00 [pmc-release]
PHST- 2023/12/17 09:42 [medline]
PHST- 2023/08/17 00:41 [pubmed]
PHST- 2023/08/16 21:22 [entrez]
AID - 7243379 [pii]
AID - uxad099 [pii]
AID - 10.1093/cei/uxad099 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2023 Dec 13;214(3):260-274. doi: 10.1093/cei/uxad099.