Involvement of phosphatidylinositol-3 kinase-Akt and nuclear factor kappa-B pathways in the effect of frutalin on human lymphocyte.
The mechanisms involved in the mitogenic effect of lectins are not fully understood and are thought to involve a cascade of intracellular signals related to T cell receptor activation. This study shows that frutalin, the alpha-D-galactose-binding lectin from Artocarpus incisa seeds, is a potent mitogenic activator of human lymphocytes. This effect is inhibited by D-galactose and PI3K inhibitors, and is accompanied by an increase in IL-2 receptor expression and by a PI3K-dependent IL-2 gene expression and IL-2 protein synthesis. Frutalin also induces Akt-phosphorylation and activates NF-kappaB, inducing its translocation from the cytosol to the nucleus. Both effects are blocked in the presence of D-galactose or by PI3K inhibitors. In summary, frutalin, interacting with alpha-D-galactose, activates signaling pathways related to TCR, and thereby triggers PI3K/Akt and NF-kappaB pathway, which modulates T cell proliferation, IL-2 synthesis and IL-2R expression. Frutalin might be a useful tool to study intracellular mechanisms following T cell activation that link upstream signaling pathways to downstream events.
Brando-Lima
Aline C
AC
Departamento de Farmacologia, Instituto de Biologia, Universidade do Estado do Rio de Janeiro, Av. 28 de setembro 87 fds, Vila Isabel, Rio de Janeiro, 20551-030, RJ, Brazil.
Saldanha-Gama
Roberta F
RF
Pereira
Cristiane Ribeiro
CR
Villela
Christina Gaspar
CG
Sampaio
André Luiz Franco
AL
Monteiro-Moreira
Ana C O
AC
Henriques
Maria das Graças M O
Md
Moreira
Renato A
RA
Barja-Fidalgo
Christina
C
D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D031622:Artocarpus; D006801:Humans; D007376:Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D037121:Plant Lectins / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D012639:Seeds; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*
D007376:Interleukin-2; D008934:Mitogens; D016328:NF-kappa B; D037121:Plant Lectins; D015375:Receptors, Interleukin-2; C043696:jacalin; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt