PMID- 27631986
OWN - NLM
STAT- MEDLINE
DCOM- 20170623
LR  - 20240216
IS  - 1553-7374 (Electronic)
IS  - 1553-7366 (Print)
IS  - 1553-7366 (Linking)
VI  - 12
IP  - 9
DP  - 2016 Sep
TI  - Progesterone-Based Therapy Protects Against Influenza by Promoting Lung Repair 
      and Recovery in Females.
PG  - e1005840
LID - 10.1371/journal.ppat.1005840 [doi]
LID - e1005840
AB  - Over 100 million women use progesterone therapies worldwide. Despite having 
      immunomodulatory and repair properties, their effects on the outcome of viral 
      diseases outside of the reproductive tract have not been evaluated. 
      Administration of exogenous progesterone (at concentrations that mimic the luteal 
      phase) to progesterone-depleted adult female mice conferred protection from both 
      lethal and sublethal influenza A virus (IAV) infection. Progesterone treatment 
      altered the inflammatory environment of the lungs, but had no effects on viral 
      load. Progesterone treatment promoted faster recovery by increasing TGF-beta, IL-6, 
      IL-22, numbers of regulatory Th17 cells expressing CD39, and cellular 
      proliferation, reducing protein leakage into the airway, improving pulmonary 
      function, and upregulating the epidermal growth factor amphiregulin (AREG) in the 
      lungs. Administration of rAREG to progesterone-depleted females promoted 
      pulmonary repair and improved the outcome of IAV infection. 
      Progesterone-treatment of AREG-deficient females could not restore protection, 
      indicating that progesterone-mediated induction of AREG caused repair in the 
      lungs and accelerated recovery from IAV infection. Repair and production of AREG 
      by damaged respiratory epithelial cell cultures in vitro was increased by 
      progesterone. Our results illustrate that progesterone is a critical host factor 
      mediating production of AREG by epithelial cells and pulmonary tissue repair 
      following infection, which has important implications for women's health.
FAU - Hall, Olivia J
AU  - Hall OJ
AUID- ORCID: 0000-0002-1981-3162
AD  - W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns 
      Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of 
      America.
FAU - Limjunyawong, Nathachit
AU  - Limjunyawong N
AUID- ORCID: 0000-0002-9540-6171
AD  - Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School 
      of Public Health, Baltimore, Maryland, United States of America.
FAU - Vermillion, Meghan S
AU  - Vermillion MS
AD  - W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns 
      Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of 
      America.
AD  - Department of Molecular and Comparative Pathobiology, The Johns Hopkins 
      University School of Medicine, Baltimore, Maryland, United States of America.
FAU - Robinson, Dionne P
AU  - Robinson DP
AD  - W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns 
      Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of 
      America.
FAU - Wohlgemuth, Nicholas
AU  - Wohlgemuth N
AUID- ORCID: 0000-0002-6450-6452
AD  - W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns 
      Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of 
      America.
FAU - Pekosz, Andrew
AU  - Pekosz A
AD  - W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns 
      Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of 
      America.
AD  - Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School 
      of Public Health, Baltimore, Maryland, United States of America.
FAU - Mitzner, Wayne
AU  - Mitzner W
AD  - Department of Environmental Health Sciences, The Johns Hopkins Bloomberg School 
      of Public Health, Baltimore, Maryland, United States of America.
FAU - Klein, Sabra L
AU  - Klein SL
AUID- ORCID: 0000-0002-0730-5224
AD  - W. Harry Feinstone Department of Molecular Microbiology and Immunology, The Johns 
      Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of 
      America.
AD  - Department of Biochemistry and Molecular Biology, The Johns Hopkins Bloomberg 
      School of Public Health, Baltimore, Maryland, United States of America.
LA  - eng
GR  - HHSN272201400007C/AI/NIAID NIH HHS/United States
GR  - R01 AI097417/AI/NIAID NIH HHS/United States
GR  - R21 AI112838/AI/NIAID NIH HHS/United States
GR  - T32 OD011089/OD/NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20160915
PL  - United States
TA  - PLoS Pathog
JT  - PLoS pathogens
JID - 101238921
RN  - 0 (Amphiregulin)
RN  - 0 (Antigens, CD)
RN  - 0 (Areg protein, mouse)
RN  - 0 (Cytokines)
RN  - EC 3.6.1.5 (Apyrase)
RN  - EC 3.6.1.5 (CD39 antigen)
SB  - IM
MH  - Amphiregulin/genetics/immunology
MH  - Animals
MH  - Antigens, CD/genetics/immunology
MH  - Apyrase/genetics/immunology
MH  - Cytokines/genetics/immunology
MH  - Female
MH  - Influenza A virus/*immunology
MH  - Lung/*immunology/pathology
MH  - Mice
MH  - Mice, Knockout
MH  - Orthomyxoviridae Infections/genetics/*immunology/pathology
MH  - Th17 Cells/*immunology/pathology
PMC - PMC5025002
COIS- The authors have declared that no competing interests exist.
EDAT- 2016/09/16 06:00
MHDA- 2017/06/24 06:00
PMCR- 2016/09/15
CRDT- 2016/09/16 06:00
PHST- 2016/06/07 00:00 [received]
PHST- 2016/08/02 00:00 [accepted]
PHST- 2016/09/16 06:00 [entrez]
PHST- 2016/09/16 06:00 [pubmed]
PHST- 2017/06/24 06:00 [medline]
PHST- 2016/09/15 00:00 [pmc-release]
AID - PPATHOGENS-D-16-01281 [pii]
AID - 10.1371/journal.ppat.1005840 [doi]
PST - epublish
SO  - PLoS Pathog. 2016 Sep 15;12(9):e1005840. doi: 10.1371/journal.ppat.1005840. 
      eCollection 2016 Sep.