PMID- 27966554
OWN - NLM
STAT- MEDLINE
DCOM- 20180326
LR  - 20230203
IS  - 1935-3456 (Electronic)
IS  - 1933-0219 (Print)
IS  - 1933-0219 (Linking)
VI  - 10
IP  - 4
DP  - 2017 Jul
TI  - IL-36 receptor deletion attenuates lung injury and decreases mortality in murine 
      influenza pneumonia.
PG  - 1043-1055
LID - 10.1038/mi.2016.107 [doi]
AB  - Influenza virus causes a respiratory disease in humans that can progress to lung 
      injury with fatal outcome. The interleukin (IL)-36 cytokines are newly described 
      IL-1 family cytokines that promote inflammatory responses via binding to the 
      IL-36 receptor (IL-36R). The mechanism of expression and the role of IL-36 
      cytokines are poorly understood. Here, we investigated the role of IL-36 
      cytokines in modulating the innate inflammatory response during influenza 
      virus-induced pneumonia in mice. The intranasal administration of influenza virus 
      upregulated IL-36alpha mRNA and protein production in the lungs. In vitro, influenza 
      virus-mediated IL-36alpha but not IL-36gamma is induced and secreted from alveolar 
      epithelial cells (AECs) through both a caspase-1 and caspase-3/7 dependent 
      pathway. IL-36alpha was detected in microparticles shed from AECs and promoted the 
      production of pro-inflammatory cytokines and chemokines in respiratory cells. 
      IL-36R-deficient mice were protected from influenza virus-induced lung injury and 
      mortality. Decreased mortality was associated with significantly reduced early 
      accumulation of neutrophils and monocytes/macrophages, activation of lymphocytes, 
      production of pro-inflammatory cytokines and chemokines, and permeability of the 
      alveolar-epithelial barrier in despite impaired viral clearance. Taken together, 
      these data indicate that IL-36 ligands exacerbate lung injury during influenza 
      virus infection.
FAU - Aoyagi, T
AU  - Aoyagi T
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, University of Michigan, Ann Arbor, Michigan, USA.
AD  - Department of Infection Control and Laboratory Diagnostics, Internal Medicine, 
      Tohoku University Graduate School of Medicine, Sendai, Japan.
FAU - Newstead, M W
AU  - Newstead MW
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, University of Michigan, Ann Arbor, Michigan, USA.
FAU - Zeng, X
AU  - Zeng X
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, University of Michigan, Ann Arbor, Michigan, USA.
FAU - Kunkel, S L
AU  - Kunkel SL
AD  - Department of Pathology, University of Michigan, Ann Arbor, Michigan, USA.
FAU - Kaku, M
AU  - Kaku M
AD  - Department of Infection Control and Laboratory Diagnostics, Internal Medicine, 
      Tohoku University Graduate School of Medicine, Sendai, Japan.
FAU - Standiford, T J
AU  - Standiford TJ
AD  - Division of Pulmonary and Critical Care Medicine, Department of Internal 
      Medicine, University of Michigan, Ann Arbor, Michigan, USA.
LA  - eng
GR  - R01 HL097564/HL/NHLBI NIH HHS/United States
GR  - R01 HL112897/HL/NHLBI NIH HHS/United States
GR  - R01 HL123515/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20161214
PL  - United States
TA  - Mucosal Immunol
JT  - Mucosal immunology
JID - 101299742
RN  - 0 (Cytokines)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Interleukin-1)
RN  - 0 (Receptors, Interleukin-1)
RN  - 0 (interleukin 1F6, mouse)
RN  - 0 (interleukin-36 receptor, mouse)
SB  - IM
MH  - Alveolar Epithelial Cells/immunology/*metabolism/virology
MH  - Animals
MH  - Cell-Derived Microparticles/metabolism
MH  - Cells, Cultured
MH  - Cytokines/metabolism
MH  - Humans
MH  - Immunity, Innate
MH  - Inflammation Mediators/metabolism
MH  - Influenza A Virus, H1N1 Subtype/*physiology
MH  - Influenza, Human/immunology
MH  - Interleukin-1/metabolism
MH  - Lung/metabolism/*pathology
MH  - Lung Injury/*immunology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Neutrophils/*immunology
MH  - Orthomyxoviridae Infections/*immunology
MH  - Receptors, Interleukin-1/genetics/*metabolism
MH  - Viral Load
PMC - PMC5471142
MID - NIHMS828139
COIS- Conflict of interest The authors declare no conflict of interests.
EDAT- 2016/12/15 06:00
MHDA- 2018/03/27 06:00
PMCR- 2017/06/19
CRDT- 2016/12/15 06:00
PHST- 2016/05/23 00:00 [received]
PHST- 2016/10/31 00:00 [accepted]
PHST- 2016/12/15 06:00 [pubmed]
PHST- 2018/03/27 06:00 [medline]
PHST- 2016/12/15 06:00 [entrez]
PHST- 2017/06/19 00:00 [pmc-release]
AID - S1933-0219(22)00712-7 [pii]
AID - 10.1038/mi.2016.107 [doi]
PST - ppublish
SO  - Mucosal Immunol. 2017 Jul;10(4):1043-1055. doi: 10.1038/mi.2016.107. Epub 2016 
      Dec 14.