PMID- 28258963
OWN - NLM
STAT- MEDLINE
DCOM- 20180426
LR  - 20180426
IS  - 1398-9995 (Electronic)
IS  - 0105-4538 (Linking)
VI  - 72
IP  - 9
DP  - 2017 Sep
TI  - Interferon-gamma-induced insufficient autophagy contributes to p62-dependent 
      apoptosis of epithelial cells in chronic rhinosinusitis with nasal polyps.
PG  - 1384-1397
LID - 10.1111/all.13153 [doi]
AB  - BACKGROUND: Autophagy is a lysosomal degradation pathway that is essential for 
      cell survival, differentiation, and homeostasis. This study aimed to investigate 
      the contribution of autophagy to the pathogenesis of CRS with nasal polyps 
      (CRSwNP). METHODS: The expression of autophagic proteins [microtubule-associated 
      protein 1 light chain 3B (LC3B)-II, autophagy-related proteins (Atg), and Beclin 
      1], substrate proteins (p62 and ubiquitinated proteins), and apoptotic signaling 
      molecules [cysteine-aspartic protease-3 and cysteine-aspartic protease-8, and 
      poly-ADP-ribose polymerase] in the sinonasal mucosa and nasal epithelial cells 
      (NECs) was detected by immunohistochemistry and Western blotting. Autophagic 
      vacuoles were observed with transmission electron microscopy. BEAS-2B cells and 
      NECs were treated with rapamycin, bafilomycin A1, or various cytokines. In some 
      experiments, cultured NECs were transfected with small interfering RNA targeting 
      p62 (sip62) or Atg5 (siAtg5). Cultured cells were analyzed with Western blotting 
      and flow cytometry. RESULTS: Although autophagic protein expression and 
      autophagic vacuole formation were increased in both eosinophilic and 
      noneosinophilic CRSwNP, particularly in NECs, there was also an up-regulation of 
      substrate proteins and apoptotic signaling molecules. IFN-gamma, but not IL-4, IL-13, 
      or IL-17A, simultaneously enhanced LC3B-II and p62 levels as well as cell 
      apoptosis in BEAS-2B cells and/or normal NECs. Bafilomycin A1 up-regulated the 
      levels of LC3B-II and p62 in polyp NECs and IFN-gamma-treated normal NECs. 
      IFN-gamma-induced apoptosis of normal NECs was exaggerated by bafilomycin A1 and 
      siAtg5. Sip62 suppressed apoptosis of polyp NECs and IFN-gamma-treated NECs. IFN-gamma 
      protein levels were increased in both eosinophilic and noneosinophilic CRSwNP. 
      CONCLUSIONS: IFN-gamma induces activated but insufficient autophagy and thus 
      contributes to a degree to p62-dependent apoptosis of NECs in CRSwNP.
CI  - (c) 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.
FAU - Wang, B-F
AU  - Wang BF
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Cao, P-P
AU  - Cao PP
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Wang, Z-C
AU  - Wang ZC
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Li, Z-Y
AU  - Li ZY
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Wang, Z-Z
AU  - Wang ZZ
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Ma, J
AU  - Ma J
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Liao, B
AU  - Liao B
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Deng, Y-K
AU  - Deng YK
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Long, X-B
AU  - Long XB
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Xu, K
AU  - Xu K
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Wang, H
AU  - Wang H
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Wang, H
AU  - Wang H
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Zeng, M
AU  - Zeng M
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Lu, X
AU  - Lu X
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
FAU - Liu, Z
AU  - Liu Z
AUID- ORCID: 0000-0002-4168-6702
AD  - Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji 
      Medical College, Huazhong University of Science and Technology, Wuhan, P.R., 
      China.
LA  - eng
PT  - Journal Article
DEP - 20170404
PL  - Denmark
TA  - Allergy
JT  - Allergy
JID - 7804028
RN  - 0 (P62 protein, human)
RN  - 0 (RNA-Binding Proteins)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Apoptosis/*drug effects
MH  - Autophagy/*drug effects
MH  - Cells, Cultured
MH  - Chronic Disease
MH  - Epithelial Cells/*cytology
MH  - Humans
MH  - Interferon-gamma/*pharmacology
MH  - Nasal Polyps/*complications
MH  - RNA-Binding Proteins/*pharmacology
MH  - Rhinitis/complications/etiology/*pathology
MH  - Sinusitis/complications/etiology/*pathology
OTO - NOTNLM
OT  - apoptosis
OT  - autophagy
OT  - epithelial cell
OT  - interferon-gamma
OT  - nasal polyps
EDAT- 2017/03/05 06:00
MHDA- 2018/04/27 06:00
CRDT- 2017/03/05 06:00
PHST- 2017/02/28 00:00 [accepted]
PHST- 2017/03/05 06:00 [pubmed]
PHST- 2018/04/27 06:00 [medline]
PHST- 2017/03/05 06:00 [entrez]
AID - 10.1111/all.13153 [doi]
PST - ppublish
SO  - Allergy. 2017 Sep;72(9):1384-1397. doi: 10.1111/all.13153. Epub 2017 Apr 4.