Adenosine-Induced NLRP11 in B Lymphoblasts Suppresses Human CD4+ T Helper Cell Responses

NLRP11 is a member of the PYD domain-containing, nucleotide-binding oligomerization-domain (NOD-) like receptor (NLR) family. The true stimulus of NLRP11 is still unclear to date, so the current study is built upon NLRP11 induction via adenosine stimulation and that activation can shape adaptive immune responses in a caspase-1-independent manner. We examined the regulation and mechanism of adenosine responsiveness via NLRP11 in human Daudi Burkitt’s B lymphoma cells and their effects on human peripheral CD4+ T lymphocytes from healthy individuals. NLRP11 was significantly upregulated after induction with adenosine at both the mRNA and protein levels, which led to the interaction of endogenous NLRP11 with the ASC adaptor protein; however, this interaction did not result in the activation of the caspase-1 enzyme. Furthermore, cocultures of NLRP11-expressing Burkitt’s lymphoma cells and naïve human peripheral CD4+ T lymphocytes had reduced IFN-γ and IL-17A production, whereas IL-13 and IL-10 cytokines did not change. Interestingly, IFN-γ and IL-17A were recovered after transfection of Burkitt’s lymphoma cells with siRNAs targeting NLRP11. Concomitant with NLRP11 upregulation, we also exhibited that adenosine A2B receptor signaling induced two phosphorylated downstream effectors, pErk1/2 and pAkt (Ser473), but not pAkt (Thr308). Taken together, our data indicate that adenosine is a negative regulator of Th1 and Th17 responses via NLRP11 in an inflammasome-independent manner.

Docetaxel hydrate induces apoptosis and suppresses tumorigenesis of oral Burkitt’s lymphoma cells (in vitro and in vivo studies)

Introduction: Burkitt’s lymphoma (BL) is one of the tumours with high malignancy and rapid cell growth, derived from B-cell lymphoma. BL typically found in children at dengue-endemic and HIV-AIDS areas with low socioeconomic levels. This study was aimed to analyse the induction of apoptosis and the suppression of tumorigenesis of oral Burkitt’s lymphoma (Raji) cells using docetaxel hydrate in vitro and in vivo. Methods: In the present study, the pure experimental laboratory with post-test only control group design was carried out. Raji cell cultures were incubated with docetaxel hydrate by doses of 0, 1.25 x 10-2, 2.5 x 10-2, and 5.0 x 10-2 M; and IC50 carboplatin (3.1 x 10-6 M) as a positive control. Induction of apoptotic was analysed by double staining of acridine orange-ethidium bromide. Tumorigenesis assay was performed by inoculating Raji cells in nude mice flanks at 1 x 106 cells/mice. Tumour treatment was delivered by various doses of docetaxel hydrate peroral. Results: Apoptosis cells were significantly increased in Raji cells treated with docetaxel hydrate by doses of 2.5 x 10-2 and 5.0 x 10-2 M. The tumour volume in mice given doses of 2.5 x 10-2 and 5.0 x 10-2 M was markedly decreasing compared to control (dose of 0). Conclusion: Docetaxel hydrate has a high antitumour potency by inhibiting tumorigenesis and increasing apoptosis of Burkitt’s lymphoma cells. Keywords: Docetaxel hydrate, double staining, Burkitt’s lymphoma cell, apoptosis, tumorigenesis