PMID- 35726645
OWN - NLM
STAT- MEDLINE
DCOM- 20220622
LR  - 20220716
IS  - 2058-7384 (Electronic)
IS  - 0394-6320 (Print)
IS  - 0394-6320 (Linking)
VI  - 36
DP  - 2022 Jan-Dec
TI  - Activation of STAT6 by intranasal allergens correlated with the development of 
      eosinophilic chronic rhinosinusitis in a mouse model.
PG  - 3946320221109529
LID - 10.1177/03946320221109529 [doi]
LID - 03946320221109529
AB  - Eosinophilic chronic rhinosinusitis (ECRS) is a chronic inflammatory disease 
      characterized by prominent eosinophilic infiltration along with a T-helper-2 
      (Th2) response. It has been well documented that signal transducer and activator 
      of transcription 6 (STAT6) is a nuclear transcription factor that mediates 
      Th2-type immunity and is implicatory of STAT1 and STAT3 in the pathogenesis of 
      allergic airway diseases. However, little is known about the association between 
      STATs and ECRS. Here, we explored the relationship between STAT1, STAT3, and/or 
      STAT6 and eosinophilic inflammation accompanied by Th2-type immunity in a mouse 
      model of ECRS. An ovalbumin (OVA)-staphylococcal enterotoxin B (SEB)-induced ECRS 
      murine model was first established. The mucosal histological alterations were 
      determined using hematoxylin and eosin staining. The number of eosinophils in 
      peripheral blood was measured using a blood cell analyzer. The cytokine (IL-4, 
      IL-5, IL17 A and IFN-gamma) expression levels in the sinonasal mucosa and total and 
      OVA-specific IgE from serum were measured using ELISA. Then, the protein levels 
      of STAT1, STAT3, STAT6, phosphorylated STAT1 (p-STAT1), p-STAT3, p-STAT6, T-box 
      expressed in T-cells (T-bet), GATA binding protein 3 (GATA-3), and retinoic acid 
      receptor-related orphan receptor gamma (RORgammat) in the sinonasal mucosa were examined 
      by immunohistochemical staining or Western blotting. Local administration of OVA 
      combined with SEB (OVA + SEB) induced multiple polyp-like lesions, accompanied by 
      prominent eosinophilic infiltration in the sinonasal mucosa. The OVA- and 
      OVA+SEB-treated groups showed significantly higher eosinophil counts from 
      peripheral blood and total and OVA-specific IgE levels from serum than those in 
      the PBS- and SEB-treated groups. The levels of p-STAT6 were markedly increased by 
      OVA + SEB exposure, as well as GATA-3, IL-4, and IL-5, but did not affect STAT6, 
      p-STAT1, p-STAT3, T-bet, RORgammat, IFN-gamma, or IL-17A. Furthermore, an eosinophil 
      count in the sinonasal mucosa showed a positive correlation with the level of 
      p-STAT6 in the ECRS mouse model. Signal transducer and activator of transcription 
      6 signaling could be activated in the OVA+SEB-induced ECRS model and might be a 
      crucial signal transducer in the development of Th2-skewed ECRS.
FAU - Wei, Hongqi
AU  - Wei H
AUID- ORCID: 0000-0003-3489-6688
AD  - Department of Otorhinolaryngology, 74566The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
AD  - Department of Otorhinolaryngology, 105860The Second Affiliated Hospital of 
      Soochow University, Suzhou, China.
FAU - Xu, Longjiang
AU  - Xu L
AD  - Department of Pathology, 105860The Second Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Sun, Peng
AU  - Sun P
AD  - Department of Otorhinolaryngology, 74566The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
FAU - Xing, Hongyu
AU  - Xing H
AD  - Department of Otorhinolaryngology, 105860The Second Affiliated Hospital of 
      Soochow University, Suzhou, China.
FAU - Zhu, Zhengwen
AU  - Zhu Z
AD  - Department of Otorhinolaryngology, 105860The Second Affiliated Hospital of 
      Soochow University, Suzhou, China.
FAU - Liu, Jisheng
AU  - Liu J
AUID- ORCID: 0000-0003-4611-8023
AD  - Department of Otorhinolaryngology, 74566The First Affiliated Hospital of Soochow 
      University, Suzhou, China.
LA  - eng
PT  - Journal Article
PL  - England
TA  - Int J Immunopathol Pharmacol
JT  - International journal of immunopathology and pharmacology
JID - 8911335
RN  - 0 (Allergens)
RN  - 0 (Interleukin-5)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 3)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (Stat6 protein, mouse)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
SB  - IM
MH  - Allergens
MH  - Animals
MH  - Disease Models, Animal
MH  - *Eosinophilia/pathology
MH  - Immunoglobulin E
MH  - Interleukin-4/metabolism
MH  - Interleukin-5/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism
MH  - Ovalbumin
MH  - *Rhinitis/pathology
MH  - *STAT6 Transcription Factor/metabolism
MH  - *Sinusitis/pathology
PMC - PMC9218454
OTO - NOTNLM
OT  - allergen
OT  - chronic rhinosinusitis
OT  - eosinophil
OT  - mouse model
OT  - signal transducer and activator of transcription
COIS- Declaration of conflicting interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2022/06/22 06:00
MHDA- 2022/06/23 06:00
PMCR- 2022/06/21
CRDT- 2022/06/21 05:13
PHST- 2022/06/21 05:13 [entrez]
PHST- 2022/06/22 06:00 [pubmed]
PHST- 2022/06/23 06:00 [medline]
PHST- 2022/06/21 00:00 [pmc-release]
AID - 10.1177_03946320221109529 [pii]
AID - 10.1177/03946320221109529 [doi]
PST - ppublish
SO  - Int J Immunopathol Pharmacol. 2022 Jan-Dec;36:3946320221109529. doi: 
      10.1177/03946320221109529.