PMID- 27561911
OWN - NLM
STAT- MEDLINE
DCOM- 20171024
LR  - 20231213
IS  - 2051-817X (Electronic)
IS  - 2051-817X (Linking)
VI  - 4
IP  - 16
DP  - 2016 Aug
TI  - ADAM17 and EGFR regulate IL-6 receptor and amphiregulin mRNA expression and 
      release in cigarette smoke-exposed primary bronchial epithelial cells from 
      patients with chronic obstructive pulmonary disease (COPD).
LID - 10.14814/phy2.12878 [doi]
LID - e12878
AB  - Aberrant activity of a disintegrin and metalloprotease 17 (ADAM17), also known as 
      TACE, and epidermal growth factor receptor (EGFR) has been suggested to 
      contribute to chronic obstructive pulmonary disease (COPD) development and 
      progression. The aim of this study was to investigate the role of these proteins 
      in activation of primary bronchial epithelial cells differentiated at the 
      air-liquid interface (ALI-PBEC) by whole cigarette smoke (CS), comparing cells 
      from COPD patients with non-COPD CS exposure of ALI-PBEC enhanced ADAM17-mediated 
      shedding of the IL-6 receptor (IL6R) and the EGFR agonist amphiregulin (AREG) 
      toward the basolateral compartment, which was more pronounced in cells from COPD 
      patients than in non-COPD controls. CS transiently increased IL6R and AREG mRNA 
      in ALI-PBEC to a similar extent in cultures from both groups, suggesting that 
      posttranslational events determine differential shedding between COPD and 
      non-COPD cultures. We show for the first time by in situ proximity ligation (PLA) 
      that CS strongly enhances interactions of phosphorylated ADAM17 with AREG and 
      IL-6R in an intracellular compartment, suggesting that CS-induced intracellular 
      trafficking events precede shedding to the extracellular compartment. Both EGFR 
      and ADAM17 activity contribute to CS-induced IL-6R and AREG protein shedding and 
      to mRNA expression, as demonstrated using selective inhibitors (AG1478 and 
      TMI-2). Our data are consistent with an autocrine-positive feedback mechanism in 
      which CS triggers shedding of EGFR agonists evoking EGFR activation, in 
      ADAM17-dependent manner, and subsequently transduce paracrine signaling toward 
      myeloid cells and connective tissue. Reducing ADAM17 and EGFR activity could 
      therefore be a therapeutic approach for the tissue remodeling and inflammation 
      observed in COPD.
CI  - (c) 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on 
      behalf of the American Physiological Society and The Physiological Society.
FAU - Stolarczyk, Marta
AU  - Stolarczyk M
AD  - Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
FAU - Amatngalim, Gimano D
AU  - Amatngalim GD
AD  - Pulmonology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
FAU - Yu, Xiao
AU  - Yu X
AD  - Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
FAU - Veltman, Mieke
AU  - Veltman M
AD  - Cell Biology, Erasmus MC, Rotterdam, The Netherlands.
FAU - Hiemstra, Pieter S
AU  - Hiemstra PS
AD  - Pulmonology, Leiden University Medical Center (LUMC), Leiden, The Netherlands.
FAU - Scholte, Bob J
AU  - Scholte BJ
AD  - Cell Biology, Erasmus MC, Rotterdam, The Netherlands b.scholte@erasmusmc.nl.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Physiol Rep
JT  - Physiological reports
JID - 101607800
RN  - 0 (Amphiregulin)
RN  - 0 (Quinazolines)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Interleukin-6)
RN  - 0 (Tyrphostins)
RN  - 170449-18-0 (RTKI cpd)
RN  - EC 2.7.10.1 (EGFR protein, human)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 3.4.24.86 (ADAM17 Protein)
RN  - EC 3.4.24.86 (ADAM17 protein, human)
SB  - IM
MH  - ADAM17 Protein/*genetics
MH  - Aged
MH  - Airway Remodeling
MH  - Amphiregulin
MH  - Bronchi/*cytology
MH  - Epithelial Cells/*metabolism
MH  - ErbB Receptors/*genetics
MH  - Female
MH  - Humans
MH  - Inhalation Exposure
MH  - Male
MH  - Middle Aged
MH  - Pulmonary Disease, Chronic Obstructive/*metabolism/physiopathology
MH  - Quinazolines/administration & dosage/adverse effects/metabolism
MH  - RNA, Messenger/*genetics
MH  - Receptors, Interleukin-6/*metabolism
MH  - Signal Transduction
MH  - Smoking/adverse effects/*metabolism
MH  - Nicotiana/adverse effects
MH  - Tyrphostins/administration & dosage/adverse effects/metabolism
PMC - PMC5002905
OTO - NOTNLM
OT  - A disintegrin and metalloprotease 17 (ADAM17)
OT  - Chronic Obstructive Pulmonary Disease (COPD)
OT  - IL6 receptor (IL6R)
OT  - TACE
OT  - amphiregulin (AREG)
OT  - epidermal growth factor receptor (EGFR)
EDAT- 2016/08/27 06:00
MHDA- 2017/10/25 06:00
PMCR- 2016/08/25
CRDT- 2016/08/27 06:00
PHST- 2016/06/13 00:00 [received]
PHST- 2016/07/09 00:00 [accepted]
PHST- 2016/08/27 06:00 [entrez]
PHST- 2016/08/27 06:00 [pubmed]
PHST- 2017/10/25 06:00 [medline]
PHST- 2016/08/25 00:00 [pmc-release]
AID - 4/16/e12878 [pii]
AID - PHY212878 [pii]
AID - 10.14814/phy2.12878 [doi]
PST - ppublish
SO  - Physiol Rep. 2016 Aug;4(16):e12878. doi: 10.14814/phy2.12878.