Expression and function of the ST2 gene in a murine model of allergic airway inflammation.
BACKGROUND
We have recently reported that soluble ST2 protein levels are elevated in the sera of patients with asthma, and correlate well with the severity of asthma exacerbation. However, the role, function, and kinetics of soluble ST2 expression in asthma remain unclear.


OBJECTIVE
The objective of the present study was to clarify the function and kinetics of soluble murine (m) ST2 expression in a murine asthma model.


METHODS
We analyzed the kinetics of gene and protein expression of mST2 in sera or lung tissue after allergen (ovalbumin; OVA) challenge in a murine model of allergic airway inflammation, the effects of mST2 protein on OVA-induced Th2 cytokine production in vitro from splenocytes of sensitized mice, and the effects of soluble mST2 on Th2-dependent allergic airway inflammation by in vivo gene transfer of mST2.


RESULTS
Serum mST2 protein levels increased to the maximal level 3 h after the allergen challenge, before serum IL-5 levels peaked. The mRNA expression of mST2 in lung tissue was induced after the allergen challenge, while that in the spleen was constitutively detected. Furthermore, pre-treatment with mST2 protein significantly inhibited the production of IL-4 and IL-5, but not IFN-gamma, from OVA-stimulated splenocytes in vitro, and intravenous mST2 gene transfer resulted in a drastic reduction in the number of eosinophils and in the levels of IL-4 and IL-5 in bronchoalveolar lavage fluid, compared with those in response to transfer of non-coding plasmid vector or of lipid alone.


CONCLUSIONS
These results suggest that increases in endogenous mST2 protein after allergen exposure may modulate Th2-mediated airway inflammation, and that in vivo gene transfer of mST2 can be applicable to use in a novel immunotherapy for allergic diseases.
Oshikawa
K
K
Division of Pulmonary Medicine, Department of Medicine, Jichi Medical School, Tochigi, Japan. kokyu2@jichi.ac.jp
Yanagisawa
K
K
Tominaga
S
S
Sugiyama
Y
Y
D000485:Allergens; D000704:Analysis of Variance; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D005260:Female; D015870:Gene Expression; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000008:administration & dosage; D007371:Interferon-gamma / Q000097:blood; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015847:Interleukin-4 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D008168:Lung / Q000378:metabolism*; D008565:Membrane Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D023421:Models, Animal; D010047:Ovalbumin; D018123:Receptors, Interleukin; D012130:Respiratory Hypersensitivity / Q000378:metabolism*
D000485:Allergens; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D015848:Interleukin-5; D008565:Membrane Proteins; D018123:Receptors, Interleukin; D015847:Interleukin-4; D007371:Interferon-gamma; D010047:Ovalbumin