Inhibition of allergen-induced eosinophil recruitment by natural tetranortriterpenoids is mediated by the suppression of IL-5, CCL11/eotaxin and NFkappaB activation

The present study reports the anti-allergic activity of a group of six different tetranortriterpenoids (TNTP) isolated from the seeds of Carapa guianensis Aublet: 6a-acetoxygedunin, 7-deacetoxy-7-oxogedunin, andirobin, methyl angolensate, 6a-acetoxyepoxyazadiradione and gedunin. Oral pretreatment wi...

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Bibliographic Details
Published in:International immunopharmacology 2006-02, Vol.6 (2), p.109-121
Main Authors: Penido, Carmen, Costa, Karina Alves, Costa, Maria Fernanda de Souza, Pereira, Jislaine de Fátima Guilhermino, Siani, Antônio Carlos, Henriques, Maria das Graças Müller de Oliveira
Format: Article
Language:English
Subjects:
Allergens - pharmacology
Animals
Blotting, Western
Cell Nucleus - chemistry
Cell Nucleus - drug effects
Cell Shape - drug effects
Chemokine CCL11
Chemokines, CC - antagonists & inhibitors
Enzyme-Linked Immunosorbent Assay
Eosinophils - drug effects
Flow Cytometry
Hypersensitivity - drug therapy
Hypersensitivity - immunology
Immunoblotting
Immunohistochemistry
Interleukin-5 - antagonists & inhibitors
Leukocytes - drug effects
Mice
Mice, Inbred C57BL
Neutrophils - drug effects
Neutrophils - ultrastructure
NF-kappa B - antagonists & inhibitors
Ovalbumin - immunology
Pleurisy - drug therapy
Pleurisy - immunology
Subcellular Fractions - drug effects
Subcellular Fractions - metabolism
Triterpenes - chemistry
Triterpenes - pharmacology
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Summary:The present study reports the anti-allergic activity of a group of six different tetranortriterpenoids (TNTP) isolated from the seeds of Carapa guianensis Aublet: 6a-acetoxygedunin, 7-deacetoxy-7-oxogedunin, andirobin, methyl angolensate, 6a-acetoxyepoxyazadiradione and gedunin. Oral pretreatment with TNTP significantly inhibited total leukocyte and eosinophil accumulation in C57BL/10 mice pleural cavities 24 h after the intrathoracic (i.t.) injection of ovalbumin (OVA), but had no effect on CD4, CD8 or gammadelta T lymphocyte accumulation. Pleural washes recovered from 6 h OVA-stimulated mice (OPW) pretreated with TNTP failed to induce shape change in eosinophil in vitro, indicating the inhibition of eosinophilotactic chemokines by TNTP. In accordance with such results, ELISA assays showed decreased levels of CCL11/eotaxin and IL-5 in OPW recovered from TNTP pretreated mice within 6 h. TNTP oral pretreatment inhibited nuclear factor-kappaB (NFkappaB) translocation into the nucleus in pleural leukocytes recovered from previously sensitized mice after antigenic challenge. In addition, the incubation of splenocytes recovered from previously sensitized mice with TNTP also inhibited NFkappaB activation after OVA stimulation. Taken together, these results indicate that the inhibition of allergic eosinophilia by TNTP is correlated with the inhibition of CCL11/eotaxin and IL-5 generation through NFkappaB signaling pathway impairment in mice.
ISSN:1567-5769