PMID- 20948165
OWN - NLM
STAT- MEDLINE
DCOM- 20110606
LR  - 20190911
IS  - 1347-8648 (Electronic)
IS  - 1347-8613 (Linking)
VI  - 114
IP  - 3
DP  - 2010
TI  - SKI-II, an inhibitor of sphingosine kinase, ameliorates antigen-induced bronchial 
      smooth muscle hyperresponsiveness, but not airway inflammation, in mice.
PG  - 304-10
AB  - To determine if endogenously generated sphingosine-1-phosphate (S1P) is involved 
      in the development of allergic bronchial asthma, the effects of systemic 
      treatments with SKI-II, a specific inhibitor of sphingosine kinase, on 
      antigen-induced bronchial smooth muscle (BSM) hyperresponsiveness and airway 
      inflammation were examined in mice. Male BALB/c mice were actively sensitized 
      with ovalbumin (OA) antigen and were repeatedly challenged with aerosolized 
      antigen. Animals also received intraperitoneal injections with SKI-II (50 mg/kg) 
      1 h prior to each antigen challenge. The acetylcholine (ACh)-induced contraction 
      of BSM isolated from the repeatedly antigen-challenged mice was significantly 
      augmented, that is, BSM hyperresponsiveness, as compared with that from the 
      control animals (P < 0.05). The BSM hyperresponsiveness induced by antigen 
      exposure was ameliorated by the systemic treatment with SKI-II, whereas the 
      treatments had no effect on BSM responsiveness to ACh in control animals. On the 
      other hand, the systemic treatments with SKI-II had no effect on antigen-induced 
      inflammatory signs, such as increase in cell counts in bronchoalveolar lavage 
      fluids (BALFs) and change in airway histology; upregulation of BALF cytokines, 
      such as interleukin-4 (IL-4) and IL-13; and elevation of total and OA-specific 
      immunoglobulin E (IgE) in sera. These findings suggest that sphingosine kinase 
      inhibitors such as SKI-II have an ability to prevent the development of BSM 
      hyperresponsiveness, but not of allergic airway inflammation. The endogenously 
      generated S1P might be one of the exacerbating factors for the airway 
      hyperresponsiveness, one of the characteristic features of allergic bronchial 
      asthma.
FAU - Chiba, Yoshihiko
AU  - Chiba Y
AD  - Department of Pharmacology, School of Pharmacy, Hoshi University, Japan. 
      chiba@hoshi.ac.jp
FAU - Takeuchi, Hiroki
AU  - Takeuchi H
FAU - Sakai, Hiroyasu
AU  - Sakai H
FAU - Misawa, Miwa
AU  - Misawa M
LA  - eng
PT  - Journal Article
DEP - 20101008
PL  - Japan
TA  - J Pharmacol Sci
JT  - Journal of pharmacological sciences
JID - 101167001
RN  - 0 (4-(4-(4-chloro-phenyl)thiazol-2-ylamino)phenol)
RN  - 0 (Antigens)
RN  - 0 (Interleukin-13)
RN  - 0 (Lysophospholipids)
RN  - 0 (Thiazoles)
RN  - 207137-56-2 (Interleukin-4)
RN  - 26993-30-6 (sphingosine 1-phosphate)
RN  - 37341-29-0 (Immunoglobulin E)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (sphingosine kinase)
RN  - NGZ37HRE42 (Sphingosine)
SB  - IM
MH  - Animals
MH  - Antigens/immunology
MH  - Asthma/*immunology/pathology
MH  - Bronchi/drug effects/immunology/metabolism
MH  - Bronchial Hyperreactivity/*drug therapy/*immunology/prevention & control
MH  - Bronchoalveolar Lavage Fluid/immunology
MH  - Immunoglobulin E/blood
MH  - Interleukin-13/analysis
MH  - Interleukin-4/analysis
MH  - Lysophospholipids/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Muscle, Smooth/drug effects/immunology/pathology
MH  - Phosphotransferases (Alcohol Group Acceptor)/*antagonists & inhibitors
MH  - Sphingosine/*analogs & derivatives/metabolism
MH  - Thiazoles/metabolism/*pharmacology
EDAT- 2010/10/16 06:00
MHDA- 2011/06/07 06:00
CRDT- 2010/10/16 06:00
PHST- 2010/10/16 06:00 [entrez]
PHST- 2010/10/16 06:00 [pubmed]
PHST- 2011/06/07 06:00 [medline]
AID - JST.JSTAGE/jphs/10202FP [pii]
AID - 10.1254/jphs.10202fp [doi]
PST - ppublish
SO  - J Pharmacol Sci. 2010;114(3):304-10. doi: 10.1254/jphs.10202fp. Epub 2010 Oct 8.