PMID- 30069878
OWN - NLM
STAT- MEDLINE
DCOM- 20190827
LR  - 20240213
IS  - 1365-2249 (Electronic)
IS  - 0009-9104 (Print)
IS  - 0009-9104 (Linking)
VI  - 194
IP  - 2
DP  - 2018 Nov
TI  - Increased beta2-adrenoceptor phosphorylation in airway smooth muscle in severe 
      asthma: possible role of mast cell-derived growth factors.
PG  - 253-258
LID - 10.1111/cei.13191 [doi]
AB  - The purpose of this study was to investigate whether growth factors produced by 
      activated human lung mast cells (HLMCs) impair beta(2) -adrenoceptor (beta(2) -AR) 
      function in human airway smooth muscle (ASM) cells. Protein array analysis 
      confirmed the presence of various growth factors, including transforming growth 
      factor (TGF)-beta1, in the supernatants of high-affinity IgE receptor 
      (FcepsilonRI)-activated HLMCs which, when applied to ASM cells, impaired 
      albuterol-induced cyclic adenosine monophosphate (cAMP) production, an effect 
      that was prevented following neutralization of TGF-beta1. This blunted beta(2) -AR 
      response was reproduced by treating ASM cells with TGF-beta1 or fibroblast growth 
      factor (FGF)-2, which induced beta(2) -AR phosphorylation at tyrosine residues 
      Tyr(141) and Tyr(350) , and significantly reduced the maximal bronchorelaxant 
      responses to isoproterenol in human precision cut lung slices (PCLS). Finally, 
      ASM cells isolated from severe asthmatics displayed constitutive elevated beta(2) 
      -AR phosphorylation at both Tyr(141) and Tyr(350) and a reduced relaxant response 
      to albuterol. This study shows for the first time that abnormal beta(2) -AR 
      phosphorylation/function in ASM cells that is induced rapidly by HLMC-derived 
      growth factors, is present constitutively in cells from severe asthmatics.
CI  - (c) 2018 British Society for Immunology.
FAU - Chachi, L
AU  - Chachi L
AD  - Department of Infection, Immunity and Inflammation, Clinical Sciences, University 
      of Leicester, Glenfield Hospital, Leicester, UK.
FAU - Alzahrani, A
AU  - Alzahrani A
AD  - Department of Infection, Immunity and Inflammation, Clinical Sciences, University 
      of Leicester, Glenfield Hospital, Leicester, UK.
AD  - Faculty of Applied Medical Sciences, Albaha University, Albaha, Kingdom of Saudi 
      Arabia.
FAU - Koziol-White, C
AU  - Koziol-White C
AD  - Rutgers Institute for Translational Medicine and Science, Rutgers Biomedical and 
      Health Sciences, Rutgers University, New Brunswick, NJ, USA.
FAU - Biddle, M
AU  - Biddle M
AD  - Department of Infection, Immunity and Inflammation, Clinical Sciences, University 
      of Leicester, Glenfield Hospital, Leicester, UK.
FAU - Bagadood, R
AU  - Bagadood R
AD  - Department of Infection, Immunity and Inflammation, Clinical Sciences, University 
      of Leicester, Glenfield Hospital, Leicester, UK.
FAU - Panettieri, R A Jr
AU  - Panettieri RA Jr
AD  - Rutgers Institute for Translational Medicine and Science, Rutgers Biomedical and 
      Health Sciences, Rutgers University, New Brunswick, NJ, USA.
FAU - Bradding, P
AU  - Bradding P
AD  - Department of Infection, Immunity and Inflammation, Clinical Sciences, University 
      of Leicester, Glenfield Hospital, Leicester, UK.
FAU - Amrani, Y
AU  - Amrani Y
AD  - Department of Infection, Immunity and Inflammation, Clinical Sciences, University 
      of Leicester, Glenfield Hospital, Leicester, UK.
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - P01 HL114471/HL/NHLBI NIH HHS/United States
GR  - 094058/WT_/Wellcome Trust/United Kingdom
GR  - DH_/Department of Health/United Kingdom
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180930
PL  - England
TA  - Clin Exp Immunol
JT  - Clinical and experimental immunology
JID - 0057202
RN  - 0 (Bronchodilator Agents)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (Receptors, IgE)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 103107-01-3 (Fibroblast Growth Factor 2)
RN  - E0399OZS9N (Cyclic AMP)
RN  - L628TT009W (Isoproterenol)
RN  - QF8SVZ843E (Albuterol)
SB  - IM
MH  - Albuterol/pharmacology
MH  - Asthma/*metabolism
MH  - Bronchodilator Agents/pharmacology
MH  - Cells, Cultured
MH  - Cyclic AMP/metabolism
MH  - Disease Progression
MH  - Fibroblast Growth Factor 2/metabolism
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/metabolism
MH  - Isoproterenol/pharmacology
MH  - Lung/drug effects/*physiology
MH  - Mast Cells/*metabolism
MH  - Myocytes, Smooth Muscle/*metabolism/pathology
MH  - Phosphorylation
MH  - Receptors, Adrenergic, beta-2/*metabolism
MH  - Receptors, IgE/metabolism
MH  - Respiratory System/*pathology
MH  - Transforming Growth Factor beta1/metabolism
PMC - PMC6194334
OTO - NOTNLM
OT  - allergy
OT  - inflammation
OT  - mast cells
OT  - signal transduction
EDAT- 2018/08/03 06:00
MHDA- 2019/08/28 06:00
PMCR- 2019/11/01
CRDT- 2018/08/03 06:00
PHST- 2018/08/03 06:00 [pubmed]
PHST- 2019/08/28 06:00 [medline]
PHST- 2018/08/03 06:00 [entrez]
PHST- 2019/11/01 00:00 [pmc-release]
AID - CEI13191 [pii]
AID - 10.1111/cei.13191 [doi]
PST - ppublish
SO  - Clin Exp Immunol. 2018 Nov;194(2):253-258. doi: 10.1111/cei.13191. Epub 2018 Sep 
      30.