PMID- 28912382
OWN - NLM
STAT- MEDLINE
DCOM- 20171206
LR  - 20230814
IS  - 1522-1504 (Electronic)
IS  - 1040-0605 (Print)
IS  - 1040-0605 (Linking)
VI  - 313
IP  - 6
DP  - 2017 Dec 1
TI  - Versican is produced by Trif- and type I interferon-dependent signaling in 
      macrophages and contributes to fine control of innate immunity in lungs.
PG  - L1069-L1086
LID - 10.1152/ajplung.00353.2017 [doi]
AB  - Growing evidence suggests that versican is important in the innate immune 
      response to lung infection. Our goal was to understand the regulation of 
      macrophage-derived versican and the role it plays in innate immunity. We first 
      defined the signaling events that regulate versican expression, using bone 
      marrow-derived macrophages (BMDMs) from mice lacking specific Toll-like receptors 
      (TLRs), TLR adaptor molecules, or the type I interferon receptor (IFNAR1). We 
      show that LPS and polyinosinic-polycytidylic acid [poly(I:C)] trigger a signaling 
      cascade involving TLR3 or TLR4, the Trif adaptor, type I interferons, and IFNAR1, 
      leading to increased expression of versican by macrophages and implicating 
      versican as an interferon-stimulated gene. The signaling events regulating 
      versican are distinct from those for hyaluronan synthase 1 (HAS1) and syndecan-4 
      in macrophages. HAS1 expression requires TLR2 and MyD88. Syndecan-4 requires 
      TLR2, TLR3, or TLR4 and both MyD88 and Trif. Neither HAS1 nor syndecan-4 is 
      dependent on type I interferons. The importance of macrophage-derived versican in 
      lungs was determined with LysM/Vcan(-/-) mice. These studies show increased 
      recovery of inflammatory cells in the bronchoalveolar lavage fluid of 
      poly(I:C)-treated LysM/Vcan(-/-) mice compared with control mice. IFN-beta and 
      IL-10, two important anti-inflammatory molecules, are significantly decreased in 
      both poly(I:C)-treated BMDMs from LysM/Vcan(-/-) mice and bronchoalveolar lavage 
      fluid from poly(I:C)-treated LysM/Vcan(-/-) mice compared with control mice. In 
      short, type I interferon signaling regulates versican expression, and versican is 
      necessary for type I interferon production. These findings suggest that 
      macrophage-derived versican is an immunomodulatory molecule with 
      anti-inflammatory properties in acute pulmonary inflammation.
CI  - Copyright (c) 2017 the American Physiological Society.
FAU - Chang, Mary Y
AU  - Chang MY
AD  - Comparative Pathology Program, Department of Comparative Medicine, University of 
      Washington School of Medicine, Seattle, Washington.
FAU - Kang, Inkyung
AU  - Kang I
AD  - Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, 
      Washington.
FAU - Gale, Michael Jr
AU  - Gale M Jr
AD  - Department of Immunology, University of Washington School of Medicine, Seattle, 
      Washington.
FAU - Manicone, Anne M
AU  - Manicone AM
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, 
      University of Washington School of Medicine, Seattle, Washington; and.
FAU - Kinsella, Michael G
AU  - Kinsella MG
AD  - Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, 
      Washington.
FAU - Braun, Kathleen R
AU  - Braun KR
AD  - Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, 
      Washington.
FAU - Wigmosta, Tara
AU  - Wigmosta T
AD  - Comparative Pathology Program, Department of Comparative Medicine, University of 
      Washington School of Medicine, Seattle, Washington.
FAU - Parks, William C
AU  - Parks WC
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, 
      University of Washington School of Medicine, Seattle, Washington; and.
AD  - Women's Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, 
      California.
FAU - Altemeier, William A
AU  - Altemeier WA
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, 
      University of Washington School of Medicine, Seattle, Washington; and.
FAU - Wight, Thomas N
AU  - Wight TN
AD  - Matrix Biology Program, Benaroya Research Institute at Virginia Mason, Seattle, 
      Washington.
FAU - Frevert, Charles W
AU  - Frevert CW
AUID- ORCID: 0000-0002-1037-3244
AD  - Comparative Pathology Program, Department of Comparative Medicine, University of 
      Washington School of Medicine, Seattle, Washington; cfrevert@uw.edu.
AD  - Division of Pulmonary and Critical Care Medicine, Department of Medicine, 
      University of Washington School of Medicine, Seattle, Washington; and.
LA  - eng
GR  - R21 RR030249/RR/NCRR NIH HHS/United States
GR  - U19 AI083019/AI/NIAID NIH HHS/United States
GR  - U19 AI125378/AI/NIAID NIH HHS/United States
GR  - R01 HL122895/HL/NHLBI NIH HHS/United States
GR  - P30 DK017047/DK/NIDDK NIH HHS/United States
GR  - R01 HL116514/HL/NHLBI NIH HHS/United States
GR  - R01 AI136468/AI/NIAID NIH HHS/United States
PT  - Journal Article
DEP - 20170914
PL  - United States
TA  - Am J Physiol Lung Cell Mol Physiol
JT  - American journal of physiology. Lung cellular and molecular physiology
JID - 100901229
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (IL10 protein, mouse)
RN  - 0 (Ifnar1 protein, mouse)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Sdc4 protein, mouse)
RN  - 0 (Syndecan-4)
RN  - 0 (TICAM-1 protein, mouse)
RN  - 0 (Toll-Like Receptors)
RN  - 0 (Vcan protein, mouse)
RN  - 0 (lipopolysaccharide, Escherichia coli O111 B4)
RN  - 126968-45-4 (Versicans)
RN  - 130068-27-8 (Interleukin-10)
RN  - 156986-95-7 (Receptor, Interferon alpha-beta)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 2.4.1.212 (Hyaluronan Synthases)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport/genetics/*immunology
MH  - Animals
MH  - Hyaluronan Synthases/genetics/immunology
MH  - *Immunity, Innate
MH  - Interferon-beta/*immunology
MH  - Interleukin-10/genetics/immunology
MH  - Lipopolysaccharides/toxicity
MH  - Lung/*immunology
MH  - Macrophages, Alveolar/*immunology
MH  - Mice
MH  - Mice, Knockout
MH  - Receptor, Interferon alpha-beta/genetics/immunology
MH  - Syndecan-4/genetics/immunology
MH  - Toll-Like Receptors/genetics/immunology
MH  - Versicans/genetics/*immunology
PMC - PMC5814701
OTO - NOTNLM
OT  - hyaluronan synthase 1
OT  - inflammation
OT  - type I interferons
OT  - versican, syndecan-4
EDAT- 2017/09/16 06:00
MHDA- 2017/12/07 06:00
PMCR- 2018/12/01
CRDT- 2017/09/16 06:00
PHST- 2017/08/08 00:00 [received]
PHST- 2017/09/07 00:00 [revised]
PHST- 2017/09/07 00:00 [accepted]
PHST- 2017/09/16 06:00 [pubmed]
PHST- 2017/12/07 06:00 [medline]
PHST- 2017/09/16 06:00 [entrez]
PHST- 2018/12/01 00:00 [pmc-release]
AID - ajplung.00353.2017 [pii]
AID - L-00353-2017 [pii]
AID - 10.1152/ajplung.00353.2017 [doi]
PST - ppublish
SO  - Am J Physiol Lung Cell Mol Physiol. 2017 Dec 1;313(6):L1069-L1086. doi: 
      10.1152/ajplung.00353.2017. Epub 2017 Sep 14.