Modulation of T lymphocyte and eosinophil functions in vitro by natural tetranortriterpenoids isolated from Carapa guianensis Aublet.
We have previously described the anti-allergic activities of a pooled fraction of tetranortriterpenoids (TNTPs) containing 6α-acetoxygedunin, 7-deacetoxy-7-oxogedunin, andirobin and methyl angolensate isolated from the seeds of Carapa guianensis. In the present study, we performed in vitro studies in order to elucidate the mechanisms by which TNTPs present their anti-allergic effects and to identify the bioactive compound(s) present in such fraction. Here, we show that in vitro incubation of eosinophils with the pooled TNTP fraction, as well as with each one of the five isolated tetranortriterpenoids, impaired the adhesion of eosinophils to tumor necrosis factor-α (TNF-α)-primed tEND.1 endothelial cells. Furthermore, the individual or pooled TNTPs impaired CCL11/eotaxin-mediated chemotaxis. By contrast, pooled TNTPs failed to inhibit adhesion and chemotaxis of T lymphocytes. However, TNTPs were able to impair anti-CD3 monoclonal antibody-induced T cell proliferation and the expression of CD25 and CD69. These data suggest that TNTPs prevent T cell activation. Pretreatment of splenocytes with the pooled TNTP fraction, as well as with each one of the five isolated TNTPs, inhibited ovalbumin (OVA)-induced in vitro production of interleukin-2, chemokine (C-C motif) ligand 11 (CCL11) and regulated on activation normal T cell expressed and secreted (RANTES, also known as CCL5). TNTPs (except 6α-acetoxygedunin) also impaired nuclear factor-κB (NFκB) nuclear translocation in OVA-challenged splenocytes. Taken together, these results demonstrate that the anti-allergic effects of TNTPs isolated from C. guianensis might rely on their ability to inhibit eosinophil migration, as well as the activation of T lymphocytes, which is shared by the five isolated TNTPs.
Laboratório de Farmacologia Aplicada, Farmanguinhos, Fundação Oswaldo Cruz, Rua Sizenando Nabuco 100, 21041-250, Rio de Janeiro, RJ, Brazil.
Fausto K
FK
Ferraris
Rodrigo
R
Rodrigues
Vagner P
VP
da Silva
Raquel
R
Figueiredo
Carmen
C
Penido
Maria das Graças M O
Md
Henriques
D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000276:immunology; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology; D004804:Eosinophils / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D005434:Flow Cytometry; D007155:Immunologic Factors / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D036701:Limonins / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D029582:Meliaceae / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D017208:Rats, Wistar; D012639:Seeds / Q000737:chemistry; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology
D007155:Immunologic Factors; D036701:Limonins; D010047:Ovalbumin