PMID- 28986735
OWN - NLM
STAT- MEDLINE
DCOM- 20181025
LR  - 20181113
IS  - 1614-7499 (Electronic)
IS  - 0944-1344 (Linking)
VI  - 24
IP  - 36
DP  - 2017 Dec
TI  - NO(2) inhalation enhances asthma susceptibility in a rat model.
PG  - 27843-27854
LID - 10.1007/s11356-017-0402-7 [doi]
AB  - Nitrogen dioxide (NO(2)) is a major air pollutant. Epidemiologic studies have 
      found that NO(2) exposure is associated with an increased risk of asthma. 
      Nevertheless, the potential molecular mechanisms remain unclear. In this study, 
      we investigated the effect of NO(2) inhalation on the occurrence of allergic 
      airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were 
      exposed to 2 and 5 mg/m(3) NO(2) (28 days, 5 h/day). The results showed that 
      NO(2) exposure could induce pulmonary inflammatory response, mucus formation, and 
      Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like 
      features. Secondly, male Wistar rats were exposed to 5 mg/m(3) NO(2) (42 days, 
      5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and 
      characterized in asthma models. Results showed that NO(2) exposure aggravated 
      lung inflammation in the OVA-sensitized rats, accompanied by the increase in 
      inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. 
      Furthermore, NO(2) exposure promoted the increase in the expression of mucin gene 
      (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1beta, intercellular 
      adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific 
      immunoglobulin E (IgE) production. Taken together, we established that NO(2) 
      exposure promotes allergic airway inflammation and increases the asthma 
      susceptibility. The underlying mechanisms involve the promotion of activation of 
      interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) 
      pathway [IL-4 receptor (IL-4R) alpha, janus kinase (JAK) 1, JAK 3, and STAT6] and 
      related transcription factor [T cell-specific protein-tyrosine kinase (Lck), 
      extracellular-regulated kinase (ERK)1/2, and nuclear factor-kappaB (NF-kappaB)]. In 
      particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon 
      (IFN)-gamma, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] 
      plays a pivotal role in NO(2)-induced inflammatory responses. These findings may 
      provide a better understanding of mechanism of NO(2)-associated respiratory 
      diseases.
FAU - Han, Ming
AU  - Han M
AD  - College of Environment and Resource, Research Center of Environment and Health, 
      Shanxi University, Taiyuan, 030006, Shanxi, People's Republic of China. 
      hanming@sxu.edu.cn.
FAU - Ji, Xiaotong
AU  - Ji X
AD  - College of Environment and Resource, Research Center of Environment and Health, 
      Shanxi University, Taiyuan, 030006, Shanxi, People's Republic of China.
FAU - Li, Guangke
AU  - Li G
AD  - College of Environment and Resource, Research Center of Environment and Health, 
      Shanxi University, Taiyuan, 030006, Shanxi, People's Republic of China. 
      liguangke@sxu.edu.cn.
FAU - Sang, Nan
AU  - Sang N
AD  - College of Environment and Resource, Research Center of Environment and Health, 
      Shanxi University, Taiyuan, 030006, Shanxi, People's Republic of China.
LA  - eng
GR  - 21477070/National Natural Science Foundation of PR China/
GR  - 21377076/National Natural Science Foundation of PR China/
GR  - 21222701/National Natural Science Foundation of PR China/
GR  - 20131401110005/Specialized Research Fund for the Doctoral Program of Higher 
      Education/
GR  - 20121401110003/Specialized Research Fund for the Doctoral Program of Higher 
      Education/
GR  - 2015021040/Natural Science Foundation of Shanxi Province/
PT  - Journal Article
DEP - 20171007
PL  - Germany
TA  - Environ Sci Pollut Res Int
JT  - Environmental science and pollution research international
JID - 9441769
RN  - 0 (Air Pollutants)
RN  - 9006-59-1 (Ovalbumin)
RN  - S7G510RUBH (Nitrogen Dioxide)
SB  - IM
MH  - Air Pollutants/*toxicity
MH  - Animals
MH  - Asthma/chemically induced/*physiopathology
MH  - Disease Models, Animal
MH  - Dose-Response Relationship, Drug
MH  - Inflammation/chemically induced/*physiopathology
MH  - Lung/immunology/*physiopathology
MH  - Male
MH  - Nitrogen Dioxide/*toxicity
MH  - Ovalbumin/*immunology/pharmacology
MH  - Rats
MH  - Rats, Wistar
OTO - NOTNLM
OT  - Airway inflammation
OT  - Allergic asthma
OT  - IL-4/STAT6 pathway
OT  - Nitrogen dioxide
OT  - Th1/Th2 differentiation
EDAT- 2017/10/08 06:00
MHDA- 2018/10/26 06:00
CRDT- 2017/10/08 06:00
PHST- 2017/02/15 00:00 [received]
PHST- 2017/10/02 00:00 [accepted]
PHST- 2017/10/08 06:00 [pubmed]
PHST- 2018/10/26 06:00 [medline]
PHST- 2017/10/08 06:00 [entrez]
AID - 10.1007/s11356-017-0402-7 [pii]
AID - 10.1007/s11356-017-0402-7 [doi]
PST - ppublish
SO  - Environ Sci Pollut Res Int. 2017 Dec;24(36):27843-27854. doi: 
      10.1007/s11356-017-0402-7. Epub 2017 Oct 7.