PMID- 25945802
OWN - NLM
STAT- MEDLINE
DCOM- 20160407
LR  - 20211119
IS  - 1535-4989 (Electronic)
IS  - 1044-1549 (Print)
IS  - 1044-1549 (Linking)
VI  - 53
IP  - 6
DP  - 2015 Dec
TI  - Brain-Derived Neurotrophic Factor Expression in Asthma. Association with Severity 
      and Type 2 Inflammatory Processes.
PG  - 844-52
LID - 10.1165/rcmb.2015-0015OC [doi]
AB  - Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family, 
      exists in several isoforms, which differentially impacts neuronal and immune cell 
      survival and differentiation. The role of BDNF and its isoforms in asthma remains 
      unclear. The objectives of this study were to compare the BDNF protein isoforms 
      and specific splice variant expression in sputum and bronchoscopic samples from 
      healthy control subjects and participants with asthma, and to relate these 
      changes to findings in IL-13-stimulated human airway epithelial cells. Sputum and 
      bronchoscopic samples from healthy control subjects and participants with asthma 
      were evaluated for BDNF protein (ELISA and Western blot) and BDNF mRNA (gel and 
      quantitative real-time PCR) in relation to asthma severity and type 2 
      inflammatory processes. BDNF mRNA was measured in cultured primary human airway 
      epithelial cells after IL-13 stimulation. Total BDNF protein differed among the 
      groups, and its mature isoform was significantly higher in sputum from subjects 
      with severe asthma compared with healthy control subjects (overall P = 0.008, 
      P = 0.027, respectively). Total BDNF was higher in those with elevated fractional 
      exhaled nitric oxide and sputum eosinophilia. In vitro, IL-13 increased BDNF exon 
      VIb splice variant and the ratio to BDNF common exon IX mRNA (P < 0.001, 
      P = 0.003, respectively). Epithelial brushing exon VIb mRNA and total BDNF 
      protein differed among the groups and were higher in subjects with severe asthma 
      than in healthy control subjects (overall P = 0.01, P = 0.02, respectively). The 
      mature BDNF isoform and the exon VIb splice variant are increased in human 
      asthmatic airways. The in vitro increase in response to IL-13 suggests that type 
      2 cytokines regulate BDNF levels and activity in asthma.
FAU - Watanabe, Tetsuya
AU  - Watanabe T
AD  - Asthma Institute at University of Pittsburgh Medical Center, Division of 
      Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - Fajt, Merritt L
AU  - Fajt ML
AUID- ORCID: 0000-0002-9143-7712
AD  - Asthma Institute at University of Pittsburgh Medical Center, Division of 
      Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - Trudeau, John B
AU  - Trudeau JB
AD  - Asthma Institute at University of Pittsburgh Medical Center, Division of 
      Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - Voraphani, Nipasiri
AU  - Voraphani N
AD  - Asthma Institute at University of Pittsburgh Medical Center, Division of 
      Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - Hu, Haizhen
AU  - Hu H
AD  - Asthma Institute at University of Pittsburgh Medical Center, Division of 
      Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - Zhou, Xiuxia
AU  - Zhou X
AD  - Asthma Institute at University of Pittsburgh Medical Center, Division of 
      Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - Holguin, Fernando
AU  - Holguin F
AD  - Asthma Institute at University of Pittsburgh Medical Center, Division of 
      Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
FAU - Wenzel, Sally E
AU  - Wenzel SE
AD  - Asthma Institute at University of Pittsburgh Medical Center, Division of 
      Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, 
      Pittsburgh, Pennsylvania.
LA  - eng
GR  - UL1 RR024153/RR/NCRR NIH HHS/United States
GR  - AI040600/AI/NIAID NIH HHS/United States
GR  - R01 HL064937/HL/NHLBI NIH HHS/United States
GR  - HL064937/HL/NHLBI NIH HHS/United States
GR  - R01 AI040600/AI/NIAID NIH HHS/United States
GR  - HL109152/HL/NHLBI NIH HHS/United States
GR  - RR024153/RR/NCRR NIH HHS/United States
GR  - U10 HL109152/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Am J Respir Cell Mol Biol
JT  - American journal of respiratory cell and molecular biology
JID - 8917225
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (IL13 protein, human)
RN  - 0 (Interleukin-13)
RN  - 0 (Protein Isoforms)
RN  - 0 (RNA, Messenger)
RN  - 7171WSG8A2 (BDNF protein, human)
SB  - IM
CIN - Am J Respir Cell Mol Biol. 2016 Feb;54(2):297-8. PMID: 26829499
CIN - Am J Respir Cell Mol Biol. 2016 Feb;54(2):297. PMID: 26829500
MH  - Adult
MH  - Asthma/*metabolism/pathology
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Bronchi/metabolism
MH  - Cells, Cultured
MH  - Exons
MH  - Female
MH  - Gene Expression
MH  - Humans
MH  - Interleukin-13/metabolism
MH  - Male
MH  - Middle Aged
MH  - Protein Isoforms/genetics/metabolism
MH  - RNA Stability
MH  - RNA, Messenger/genetics/metabolism
MH  - Severity of Illness Index
MH  - Sputum/metabolism
MH  - Young Adult
PMC - PMC4742942
OTO - NOTNLM
OT  - IL-13
OT  - asthma
OT  - brain-derived neurotrophic factor
OT  - epithelial cells
OT  - sputum
EDAT- 2015/05/07 06:00
MHDA- 2016/04/08 06:00
PMCR- 2016/12/01
CRDT- 2015/05/07 06:00
PHST- 2015/05/07 06:00 [entrez]
PHST- 2015/05/07 06:00 [pubmed]
PHST- 2016/04/08 06:00 [medline]
PHST- 2016/12/01 00:00 [pmc-release]
AID - 10.1165/rcmb.2015-0015OC [doi]
PST - ppublish
SO  - Am J Respir Cell Mol Biol. 2015 Dec;53(6):844-52. doi: 10.1165/rcmb.2015-0015OC.