The role of sphingosine kinase in a murine model of allergic asthma.
In: Journal of immunology (Baltimore, Md. : 1950), Jg. 180 (2008-03-15), Heft 6, S. 4323-9
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Zugriff:
Asthma is an allergic disease characterized by chronic airway eosinophilia and pulmonary infiltration of lymphocytes, particularly of the Th2 subtype, macrophages and mast cells. Previous studies have shown a pivotal role for sphingosine kinase (SphK) on various proinflammatory cells, such as lymphocyte and eosinophil migration and mast cell degranulation. We therefore examined the roles of SphK in a murine model of allergic asthma. In mice previously sensitized to OVA, i.p. administration of N,N-dimethylsphingosine (DMS), a potent SphK inhibitor, significantly reduced the total inflammatory cell infiltrate and eosinophilia and the IL-4, IL-5, and eotaxin levels in bronchoalveolar lavage fluid in response to inhaled OVA challenge. In addition, DMS significantly suppressed OVA-induced inflammatory infiltrates and mucus production in the lungs, and airway hyperresponsiveness to methacholine in a dose-dependent manner. OVA-induced lymphocyte proliferation and IL-4 and IL-5 secretion were reduced in thoracic lymph node cultures from DMS-treated mice. Moreover, similar reduction in inflammatory infiltrates, bronchoalveolar lavage, IL-4, IL-5, eotaxin, and serum OVA-specific IgE levels was observed in mice with SphK1 knock-down via small interfering RNA approach. Together, these data demonstrate the therapeutic potential of SphK modulation in allergic airways disease.
Titel: |
The role of sphingosine kinase in a murine model of allergic asthma.
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Autor/in / Beteiligte Person: | Lai, WQ ; Goh, HH ; Bao, Z ; Wong, WS ; Melendez, AJ ; Leung, BP |
Zeitschrift: | Journal of immunology (Baltimore, Md. : 1950), Jg. 180 (2008-03-15), Heft 6, S. 4323-9 |
Veröffentlichung: | Bethesda, MD : American Association of Immunologists ; <i>Original Publication</i>: Baltimore : Williams & Wilkins, c1950-, 2008 |
Medientyp: | academicJournal |
ISSN: | 0022-1767 (print) |
DOI: | 10.4049/jimmunol.180.6.4323 |
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