PMID- 30031725
OWN - NLM
STAT- MEDLINE
DCOM- 20190812
LR  - 20191002
IS  - 1525-2191 (Electronic)
IS  - 0002-9440 (Print)
IS  - 0002-9440 (Linking)
VI  - 188
IP  - 10
DP  - 2018 Oct
TI  - IL-1beta Stimulates Brain-Derived Neurotrophic Factor Production in Eutopic 
      Endometriosis Stromal Cell Cultures: A Model for Cytokine Regulation of 
      Neuroangiogenesis.
PG  - 2281-2292
LID - S0002-9440(18)30097-X [pii]
LID - 10.1016/j.ajpath.2018.06.011 [doi]
AB  - Endometriosis implants are comprised of glandular and stromal elements, 
      macrophages, nerves, and blood vessels and are commonly accompanied by pelvic 
      pain. We propose that activated macrophages are recruited to and infiltrate 
      nascent lesions, where they secrete proinflammatory cytokines, promoting the 
      production of chemokines, neurotrophins, and angiogenic growth factors that 
      sustain an inflammatory microenvironment. Immunohistochemical evaluation of 
      endometriosis lesions reveals in situ colocalization of concentrated macrophages, 
      brain-derived neurotrophic factor (BDNF), and nerve fibers. These observations 
      were coupled with biochemical analyses of primary eutopic endometriosis stromal 
      cell (EESC) cultures, which allowed defining potential pathways leading to the 
      neuroangiogenic phenotype of these lesions. Our findings indicate that IL-1beta 
      potently (EC(50) = 7 +/- 2 ng/mL) stimulates production of EESC BDNF at the mRNA 
      and protein levels in an IL-1 receptor-dependent fashion. Selective kinase 
      inhibitors demonstrate that this IL-1beta effect is mediated by c-Jun N-terminal 
      kinase (JNK), NF-kappaB, and mechanistic target of rapamycin signal transduction 
      pathways. IL-1beta regulation of regulated on activation normal T cell expressed and 
      secreted (RANTES), a prominent EESC chemokine, also relies on JNK and NF-kappaB. An 
      important clinical implication of the study is that interference with BDNF and 
      RANTES production, by selectively targeting the JNK and NF-kappaB cascades, may offer 
      a tractable therapeutic strategy to mitigate the pain and inflammation associated 
      with endometriosis.
CI  - Copyright (c) 2018 American Society for Investigative Pathology. Published by 
      Elsevier Inc. All rights reserved.
FAU - Yu, Jie
AU  - Yu J
AD  - Department of Obstetrics and Gynecology, Wake Forest School of Medicine, 
      Winston-Salem, North Carolina.
FAU - Francisco, Antonio M C
AU  - Francisco AMC
AD  - Department of Obstetrics and Gynecology, Wake Forest School of Medicine, 
      Winston-Salem, North Carolina; Health Sciences School, University of Vale do 
      Sapucai, Pouso Alegre, Brazil.
FAU - Patel, Bansari G
AU  - Patel BG
AD  - Department of Obstetrics and Gynecology, Wake Forest School of Medicine, 
      Winston-Salem, North Carolina.
FAU - Cline, J Mark
AU  - Cline JM
AD  - Department of Comparative Medicine, Wake Forest School of Medicine, 
      Winston-Salem, North Carolina; Molecular Medicine and Translational Sciences 
      Program, Wake Forest School of Medicine, Winston-Salem, North Carolina.
FAU - Zou, Eric
AU  - Zou E
AD  - Department of Obstetrics and Gynecology, Wake Forest School of Medicine, 
      Winston-Salem, North Carolina.
FAU - Berga, Sarah L
AU  - Berga SL
AD  - Department of Obstetrics and Gynecology, Wake Forest School of Medicine, 
      Winston-Salem, North Carolina.
FAU - Taylor, Robert N
AU  - Taylor RN
AD  - Department of Obstetrics and Gynecology, Wake Forest School of Medicine, 
      Winston-Salem, North Carolina; Molecular Medicine and Translational Sciences 
      Program, Wake Forest School of Medicine, Winston-Salem, North Carolina; Clinical 
      and Translational Science Institute, Wake Forest School of Medicine, 
      Winston-Salem, North Carolina. Electronic address: rob.taylor@hsc.utah.edu.
LA  - eng
GR  - R21 HD078818/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20180720
PL  - United States
TA  - Am J Pathol
JT  - The American journal of pathology
JID - 0370502
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Chemokine CCL5)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (NF-kappa B)
RN  - EC 2.7.12.2 (MAP Kinase Kinase 4)
MH  - Adult
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - Cells, Cultured
MH  - Chemokine CCL5/metabolism
MH  - Cytokines/*physiology
MH  - Endometriosis/*physiopathology
MH  - Female
MH  - Humans
MH  - Interleukin-1beta/*pharmacology
MH  - MAP Kinase Kinase 4/metabolism
MH  - Macrophages/metabolism/physiology
MH  - NF-kappa B/metabolism
MH  - Neovascularization, Pathologic/physiopathology
MH  - Neurogenesis/physiology
MH  - Stromal Cells/metabolism/physiology
MH  - Young Adult
PMC - PMC6169127
EDAT- 2018/07/23 06:00
MHDA- 2019/08/14 06:00
PMCR- 2019/10/01
CRDT- 2018/07/23 06:00
PHST- 2018/01/28 00:00 [received]
PHST- 2018/05/15 00:00 [revised]
PHST- 2018/06/11 00:00 [accepted]
PHST- 2018/07/23 06:00 [pubmed]
PHST- 2019/08/14 06:00 [medline]
PHST- 2018/07/23 06:00 [entrez]
PHST- 2019/10/01 00:00 [pmc-release]
AID - S0002-9440(18)30097-X [pii]
AID - 10.1016/j.ajpath.2018.06.011 [doi]
PST - ppublish
SO  - Am J Pathol. 2018 Oct;188(10):2281-2292. doi: 10.1016/j.ajpath.2018.06.011. Epub 
      2018 Jul 20.