Rituximab (chimeric anti- @entity2225 monoclonal antibodies) is currently being used in the treatment of B @entity1893 ( @entity1893 ). We have recently reported that @entity2408 triggers and modifies various intracellular signaling pathways in @entity1893 B-cell lines, resulting in reverting the chemoresistant phenotype to a sensitive phenotype. This study investigated whether rituximab also modifies intracellular signaling pathways resulting in the sensitization of @entity1893 cells to Fas-induced apoptosis. Treatment of the Fas-resistant @entity1893 cell lines (2F7, Ramos and Raji) with rituximab sensitized the cells to @entity10762 ( @entity12 agonist mAb)-induced apoptosis and synergy was achieved. Fas expression was upregulated by rituximab as early as 6 h post-treatment as determined by flow cytometry, reverse transcriptase-polymerase chain reaction and Western blot. Rituximab inhibited both the expression and activity of the transcription repressor @entity19767 ( @entity19767 ) that negatively regulates Fas transcription. Inhibition of @entity19767 resulted in the upregulation of Fas expression and sensitization of the @entity5 cells to @entity10762 -induced apoptosis. The downregulation of @entity19767 expression was the result of rituximab-induced inhibition of both the @entity1435 (MAPK) signaling pathway and constitutive nuclear factor kappa of B cells (NF-kappaB) activity. The involvement of NF-kappaB and @entity19767 in the regulation of Fas expression was corroborated by the use of Ramos cells with a dominant-active inhibitor of NF-kappaB (Ramos IkappaB- @entity172 receptor (ER) mutant) and by silencing @entity19767 with @entity19767 siRNA, respectively. Further, the role of rituximab-mediated inhibition of the p38 MAPK/ @entity68172 pathway in the regulation of Fas and sensitization to @entity10762 -induced apoptosis was validated by the use of specific chemical inhibitors of this pathway and which mimicked rituximab-mediated effects. These findings provide a novel mechanism of rituximab-mediated activity by sensitizing @entity1893 cells to Fas-induced apoptosis.

Rituximab (chimeric anti- @entity2225 ) sensitizes XXXX cell lines to Fas-induced apoptosis.

@entity172 :: ('MESH:D004967', 'Chemical') :: ['estrogen'] @entity2408 :: ('CHEBI:64357', 'Chemical') :: ['rituximab'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor'] @entity2225 :: ('54474', 'Gene') :: ['CD20'] @entity12 :: ('356', 'Gene') :: ['FasL'] @entity19767 :: ('7528', 'Gene') :: ['Yin-Yang 1', 'YY1'] @entity1435 :: ('1432', 'Gene') :: ['p38 mitogen-activated protein kinase'] @entity1893 :: ('MESH:D008228', 'Disease') :: ["non-Hodgkin's lymphoma", 'NHL'] @entity10762 :: ('MESH:C418965', 'Chemical') :: ['CH-11'] @entity68172 :: ('4790;7528', 'Gene') :: ['NF-kappaB/YY1']
@entity1893 :: (MESH:D008228,Disease) :: ['B-NHL']
