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 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.
Penido
Carmen
C
Departamento de Farmacologia Aplicada, Far-Manguinhos, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, 21041-250, Rio de Janeiro, RJ, Brazil.
Costa
Karina Alves
KA
Costa
Maria Fernanda de Souza
MF
Pereira
Jislaine de Fátima Guilhermino
Jde F
Siani
Antônio Carlos
AC
Henriques
Maria das Graças Müller de Oliveira
Md
D000485:Allergens / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects; D048430:Cell Shape / Q000187:drug effects; D054413:Chemokine CCL11; D019742:Chemokines, CC / Q000037:antagonists & inhibitors*; D004797:Enzyme-Linked Immunosorbent Assay; D004804:Eosinophils / Q000187:drug effects*; D005434:Flow Cytometry; D006967:Hypersensitivity / Q000188:drug therapy* / Q000276:immunology; D015151:Immunoblotting; D007150:Immunohistochemistry; D015848:Interleukin-5 / Q000037:antagonists & inhibitors*; D007962:Leukocytes / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors*; D009504:Neutrophils / Q000187:drug effects / Q000648:ultrastructure; D010047:Ovalbumin / Q000276:immunology; D010998:Pleurisy / Q000188:drug therapy / Q000276:immunology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D000485:Allergens; C515457:Ccl11 protein, mouse; D054413:Chemokine CCL11; D019742:Chemokines, CC; D015848:Interleukin-5; D016328:NF-kappa B; D014315:Triterpenes; D010047:Ovalbumin