PMID- 37742576
OWN - NLM
STAT- Publisher
LR  - 20231012
IS  - 1090-2414 (Electronic)
IS  - 0147-6513 (Linking)
VI  - 265
DP  - 2023 Oct 15
TI  - Role of NLRP3 in the exacerbation of ozone-induced allergic rhinitis.
PG  - 115506
LID - S0147-6513(23)01010-2 [pii]
LID - 10.1016/j.ecoenv.2023.115506 [doi]
AB  - OBJECTIVE: Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated 
      inflammatory disorder of the nasal mucosa, and the impact of ozone on AR is 
      gaining increasing attention. Although NOD-like receptor thermal protein domain 
      associated protein 3 (NLRP3) plays a crucial role in the pathogenesis of AR, its 
      regulatory mechanisms in ozone-induced exacerbation remain unclear. Therefore, we 
      explored the impact of ozone inhalation on inflammation in AR and investigated 
      the regulatory mechanisms involving NLRP3. METHODS: Fifty female Sprague-Dawley 
      rats were selected and divided into five groups: normal control (NC), normal with 
      ozone exposure (NE), AR model, AR with ozone exposure (ARE), and ARE treated with 
      the NLRP3 inhibitor MCC950 (ARE+MCC950). Behavioral changes were observed in the 
      rats, and the expression of NLRP3, active-caspase 1, and GSDMD-N was detected by 
      western blotting. The expression levels of interleukin (IL)- 4, IL-5, IL-13, 
      IL-1beta, and ovalbumin-specific IgE (OVA-sIgE) in nasal lavage fluid as well as 
      IL-6 in the serum were measured by ELISA. The expression and distribution of 
      NLRP3 and IL-1beta in nasal mucosal tissue were detected by immunohistochemistry, 
      and pathological changes and eosinophilic infiltration in nasal mucosal tissue 
      were observed by hematoxylin and eosin (HE) staining. The effects of ozone 
      exposure on inflammation in the nasal mucosal tissue of rats with AR and the 
      relationship between NLRP3 and inflammation were analyzed. RESULTS: Upregulation 
      of NLRP3 was observed in the AR rat model, and ozone further aggravated the 
      expression of NLRP3 in the nasal mucosal tissue. Compared to the AR, NC, and NE 
      groups, NLRP3 inflammasomes were activated in the ARE group, and the expression 
      levels of related indexes active-caspase 1 and GSDMD-N were significantly 
      increased; the expression levels of Th2 inflammatory factors IL-4, IL-5, IL-13, 
      and OVA-sIgE were increased, and inflammatory factors such as IL-1beta and IL-6 
      expression was also significantly increased. HE staining revealed that ozone 
      aggravated damage to the nasal mucosal tissue in AR. Compared with the ARE group, 
      the expression of NLRP3 inflammasomes was downregulated, sneezing and scratching 
      symptoms were reduced, inflammatory indicators in nasal lavage fluid were 
      decreased, and nasal mucosal tissue damage was alleviated in rats in the 
      ARE+MCC950 group. CONCLUSION: Ozone exposure significantly increased the 
      inflammatory response in an animal model of AR. MCC950 can selectively inhibit 
      the expression of NLRP3, inhibit the activity of inflammasomes, and reduce nasal 
      mucosal inflammation by regulating the NLRP3-caspase-1-IL-1beta pathway.
CI  - Copyright (c) 2023 The Authors. Published by Elsevier Inc. All rights reserved.
FAU - Zhang, Xueyan
AU  - Zhang X
AD  - Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai, 
      China.
FAU - Sun, Na
AU  - Sun N
AD  - Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai, 
      China.
FAU - Huang, Yu
AU  - Huang Y
AD  - Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai, 
      China.
FAU - Duan, Yusen
AU  - Duan Y
AD  - Shanghai Environmental Monitoring Center, Shanghai, China.
FAU - Zhang, Ruxin
AU  - Zhang R
AD  - Department of Otolaryngology, Huadong Hospital, Fudan University, Shanghai, 
      China. Electronic address: zhangruxin@hotmail.com.
LA  - eng
PT  - Journal Article
DEP - 20230923
PL  - Netherlands
TA  - Ecotoxicol Environ Saf
JT  - Ecotoxicology and environmental safety
JID - 7805381
SB  - IM
OTO - NOTNLM
OT  - Allergic rhinitis
OT  - IL-1beta
OT  - Inflammatory response
OT  - NLRP3
OT  - Ozone
COIS- Declaration of Competing Interest The authors declare the following financial 
      interests/personal relationships which may be considered as potential competing 
      interests: Ruxin Zhang reports financial support was provided by National Natural 
      Science Foundation of China.
EDAT- 2023/09/25 00:42
MHDA- 2023/09/25 00:42
CRDT- 2023/09/24 18:11
PHST- 2023/06/02 00:00 [received]
PHST- 2023/08/31 00:00 [revised]
PHST- 2023/09/18 00:00 [accepted]
PHST- 2023/09/25 00:42 [pubmed]
PHST- 2023/09/25 00:42 [medline]
PHST- 2023/09/24 18:11 [entrez]
AID - S0147-6513(23)01010-2 [pii]
AID - 10.1016/j.ecoenv.2023.115506 [doi]
PST - ppublish
SO  - Ecotoxicol Environ Saf. 2023 Oct 15;265:115506. doi: 
      10.1016/j.ecoenv.2023.115506. Epub 2023 Sep 23.