RIP1 has a role in CD40-mediated apoptosis in human follicular lymphoma cells

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Adem , J , Eray , M , Eeva , J , Nuutinen , U & Pelkonen , J 2017 , ' RIP1 has a role in CD40-mediated apoptosis in human follicular lymphoma cells ' , Immunobiology , vol. 11 , pp. 998-1003 .

Title: RIP1 has a role in CD40-mediated apoptosis in human follicular lymphoma cells
Author: Adem, Jemal; Eray, Mine; Eeva, Jonna; Nuutinen, Ulla; Pelkonen, Jukka
Contributor organization: HUSLAB
University of Helsinki
Department of Pathology
Date: 2017-11
Language: eng
Number of pages: 6
Belongs to series: Immunobiology
ISSN: 0171-2985
Abstract: CD40 is a cell surface receptor which belongs to tumor necrosis factor receptor (TNFR) family members. It transmits signals that regulate diverse cellular responses such as proliferation, differentiation, adhesion molecule expression and apoptosis. Unlike other TNFR family members (TRAIL-R, Fas-R and TNFR1), the CD40 cytoplasmic tail lacks death domain. However, CD40 is capable of inducing apoptosis in different types of cancer cells including lymphoma. The apoptotic effect of CD40 is linked to the involvement of Fas, TRAIL or receptor interacting protein 1 (RIP1) kinase. We have previously shown that CD40 activation has anti-apoptotic or apoptotic effect in follicular lymphoma (FL) cell lines. In this study, we investigated the mechanism by which CD40 mediates apoptosis in a follicular lymphoma cell line, HF4.9. We show here that CD40-induced apoptosis was dependent on caspase-8 activation because caspase-8 specific inhibitor, Z-IETD-FMK completely prevented apoptosis. Therefore, the involvement of TRAIL, Fas and RIP1 in caspase-8 activation was examined. The exogenous TRAIL-induced apoptosis was fully prevented by anti-TRAIL neutralizing antibody. However, the antibody had no effect on CD40-induced apoptosis indicating that CD40 did not induce the expression of endogenous TRAIL in HF4.9 cells. Moreover, the cells were not sensitive to Fas-mediated apoptosis. Interestingly, RIP1 specific inhibitor, necrostatin-1 decreased CD40-induced apoptosis, which showed that RIP1 has a role in caspase-8 activation. In conclusion, the survival or apoptotic effects of CD40-mediated signaling might be related to the differentiation stages of FL cells.
Subject: RIP1
follicular lymphoma
TNFR family member
3111 Biomedicine
Peer reviewed: Yes
Usage restriction: openAccess
Self-archived version: publishedVersion

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