PMID- 19493441
OWN - NLM
STAT- MEDLINE
DCOM- 20091008
LR  - 20181201
IS  - 2542-5641 (Electronic)
IS  - 0366-6999 (Linking)
VI  - 122
IP  - 9
DP  - 2009 May 5
TI  - Inhibitory effects of sunitinib on ovalbumin-induced chronic experimental asthma 
      in mice.
PG  - 1061-6
AB  - BACKGROUND: Tyrosine kinase signaling cascades play a critical role in the 
      pathogenesis of allergic airway inflammation. Sunitinib, a multitargeted receptor 
      tyrosine kinase inhibitor, has been reported to exert potent immunoregulatory, 
      anti-inflammatory and anti-fibrosis effects. We investigated whether sunitinib 
      could suppress the progression of airway inflammation, airway hyperresponsiveness 
      (AHR), and airway remodeling in a murine model of chronic asthma. METHODS: 
      Ovalbumin (OVA)-sensitized mice were chronically challenged with aerosolized OVA 
      for 8 weeks. Some mice were intragastrically administered with sunitinib (40 
      mg/kg) daily during the period of OVA challenge. Twelve hours after the last OVA 
      challenge, mice were evaluated for the development of airway inflammation, AHR 
      and airway remodeling. The levels of total serum immunoglobulin E (IgE) and Th2 
      cytokines (interleukin (IL)-4 and IL-13) in bronchoalveolar lavage fluid (BALF) 
      were measured by ELISA. The expression of phosphorylated c-kit protein in the 
      lungs was detected by immunoprecipitation/Western blotting (IP/WB) analysis. 
      RESULTS: Sunitinib significantly inhibited eosinophilic airway inflammation, 
      persistent AHR and airway remodeling in chronic experimental asthma. It reduced 
      levels of total serum IgE and BALF Th2 cytokines and also lowered the expression 
      of phosphorylated c-kit protein in remodelled airways. CONCLUSIONS: Sunitinib may 
      inhibit the development of airway inflammation, AHR and airway remodeling. It is 
      potentially beneficial to the prevention or treatment of asthma.
FAU - Huang, Mao
AU  - Huang M
AD  - Department of Respiratory Medicine, First Affiliated Hospital, Nanjing Medical 
      University, Nanjing, Jiangsu, China. hm6114@126.com
FAU - Liu, Xuan
AU  - Liu X
FAU - DU, Qiang
AU  - DU Q
FAU - Yao, Xin
AU  - Yao X
FAU - Yin, Kai-sheng
AU  - Yin KS
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - China
TA  - Chin Med J (Engl)
JT  - Chinese medical journal
JID - 7513795
RN  - 0 (Angiogenesis Inhibitors)
RN  - 0 (Indoles)
RN  - 0 (Interleukin-13)
RN  - 0 (Pyrroles)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - V99T50803M (Sunitinib)
SB  - IM
MH  - Angiogenesis Inhibitors/*pharmacology
MH  - Animals
MH  - Asthma/*chemically induced/*drug therapy/immunology
MH  - Blotting, Western
MH  - Bronchial Hyperreactivity/chemically induced/immunology
MH  - Bronchoalveolar Lavage Fluid/chemistry
MH  - Female
MH  - Immunoglobulin E/blood
MH  - Immunohistochemistry
MH  - Immunoprecipitation
MH  - In Vitro Techniques
MH  - Indoles/*pharmacology
MH  - Inflammation/chemically induced/immunology
MH  - Interleukin-13/metabolism
MH  - Interleukin-4/metabolism
MH  - Lung/*drug effects/immunology/metabolism
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Ovalbumin/*pharmacology
MH  - Proto-Oncogene Proteins c-kit/metabolism
MH  - Pyrroles/*pharmacology
MH  - Sunitinib
EDAT- 2009/06/06 09:00
MHDA- 2009/10/09 06:00
CRDT- 2009/06/05 09:00
PHST- 2009/06/05 09:00 [entrez]
PHST- 2009/06/06 09:00 [pubmed]
PHST- 2009/10/09 06:00 [medline]
PST - ppublish
SO  - Chin Med J (Engl). 2009 May 5;122(9):1061-6.