RESUMEN
Curcumin is a phenolic natural product isolated from the rhizome of Curcuma longa (tumeric). It was previously described that curcumin had a potent anti-inflammatory effect and inhibited the proliferation of a variety of tumor cells. In the present study, we investigated the inhibitory effects of curcumin on the response of normal murine splenic B cells. Curcumin inhibited the proliferative response of purified splenic B cells from BALB/c mice stimulated with the Toll-like receptor ligands LPS and CpG oligodeoxynucleotides. LPS-induced IgM secretion was also inhibited by curcumin. The proliferative response induced by either the T-independent type 2 stimuli anti-delta-dextran or anti-IgM antibodies was relatively resistant to the effect of curcumin. We investigated the intracellular signaling events involved in the inhibitory effects of curcumin on murine B cells. Curcumin did not inhibit the increase in calcium levels induced by anti-IgM antibody. Western blotting analysis showed that curcumin inhibited TLR ligands and anti-IgM-induced phosphorylation of ERK, IkappaB and p38. Curcumin also decreased the nuclear levels of NFkappaB. Our results suggested that curcumin is an important inhibitor of signaling pathways activated upon B cell stimulation by TLR ligands. These data indicate that curcumin could be a potent pharmacological inhibitor of B cell activation.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Linfocitos B/efectos de los fármacos , Curcumina/farmacología , Transducción de Señal/efectos de los fármacos , Receptores Toll-Like/metabolismo , Animales , Anticuerpos Antiidiotipos , Linfocitos B/metabolismo , Calcio/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Curcuma , Femenino , Ligandos , Masculino , Ratones , Ratones Endogámicos BALB CRESUMEN
In the present study, we investigated whether natural killer (NK) cells modulate immunoglobulin (Ig) secretion by B cells from Trypanosoma cruzi-infected mice. B cells from infected mice increased IgM and IgG2a secretion in the presence of a NK cell line, and this response was cell contact-dependent. Stimulation of splenic B cells with polyinosinic-polycytidylic acid, a NK cell activator, also increased Ig secretion by B cells from infected mice. B cells from infected mice expressed higher levels of the B7.2 molecule. Our results suggest that NK cells may be involved in the control of the abnormal B cell activation observed during T. cruzi infection.
Asunto(s)
Anticuerpos Antiprotozoarios/análisis , Linfocitos B/inmunología , Enfermedad de Chagas/inmunología , Trypanosoma cruzi/inmunología , Animales , Antígenos CD/análisis , Linfocitos B/efectos de los fármacos , Antígeno B7-2 , Células Cultivadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Citometría de Flujo , Inmunoglobulina G/análisis , Inmunoglobulina M/análisis , Células Asesinas Naturales/inmunología , Lipopolisacáridos/farmacología , Activación de Linfocitos , Masculino , Glicoproteínas de Membrana/análisis , Ratones , Ratones Endogámicos BALB C , Poli I-C/farmacologíaRESUMEN
A regulatory function for CD4 molecules in lymphocyte adhesion and motility was investigated. Murine splenic CD4+ T cells, activated in the presence of phorbol ester and immobilized anti-CD4 mAb, adhered to the plastic surface and formed extended cytoplasmic projections (pseudopodia). Pseudopod formation was cell-density-dependent, peaked at Day 3, and disappeared by Day 5 in culture. This response could be inhibited by soluble anti-CD4 and by RGD-containing peptide. Ligation of CD4 was required at a late stage in cell activation, and stimulated cell motility in vitro. Addition of IL-4, but not IL-2, upregulated pseudopod formation induced by suboptimal stimuli. Anti-IL-4 mAb blocked pseudopod formation, and exogenous IL-4 restored the response. A combination of IL-4 plus phorbol ester, but not IL-2 plus phorbol ester, induced pseudopod formation in concert with CD4 ligation. Exogenous IL-2, on the other hand, blocked pseudopod formation. CD45RBlow CD4+ T cells were much more efficient than CD45RBhigh CD4+ T cells for pseudopod formation. These results indicate that CD4 ligation induces CD4+ T-cell adhesion and motility, mainly in the memory/activated subset, which might be relevant for immune responses in vivo.
Asunto(s)
Antígenos CD4/inmunología , Linfocitos T CD4-Positivos/inmunología , Adhesión Celular , Seudópodos , Animales , Recuento de Células , Movimiento Celular , Células Cultivadas , Memoria Inmunológica , Interleucina-4/inmunología , Activación de Linfocitos , Ratones , Ratones Endogámicos BALB C , Bazo/citología , Bazo/inmunologíaRESUMEN
This study describes the production and action of interferon in mice infected with Colombian and Y strain T. cruzi. The production of interferon was monitored by an in vitro assay of plasma and extract of spleen, lung and heart for interferon activity. The action of interferon in mice was assessed by measuring an interferon-mediated enzyme activity, 2-5A synthetase. Infected mice (strain Balb/c) were sacrificed at different time intervals, and the level of this enzyme was measured in extracts of spleen, lung and heart. Colombian strain infection induced higher levels of interferon than Y strain under the same conditions; consequently, a greater increase in 2-5A synthetase induction was observed in the former of the two strains. These results suggest that interferon produced by T. cruzi infected mice is active, since a variety of organs respond to its presence by producing elevated levels of 2-5A synthetase.