Chemotherapy-triggered cathepsin B release in myeloid-derived suppressor cells activates the Nlrp3 inflammasome and promotes tumor growth
International audience; Chemotherapeutic agents are widely used for cancer treatment. In addition to their direct cytotoxic effects, these agents harness the host's immune system, which contributes to their antitumor activity. Here we show that two clinically used chemotherapeutic agents, gemcitabine (Gem) and 5-fluorouracil (5FU), activate the NOD-like receptor family, pyrin domain containing-3 protein (Nlrp3)-dependent caspase-1 activation complex (termed the inflammasome) in myeloid-derived suppressor cells (MDSCs), leading to production of interleukin-1β (IL-1β), which curtails anticancer immunity. Chemotherapy-triggered IL-1β secretion relied on lysosomal permeabilization and the relea…
Evolution of ecdysteroids and of their apolar conjugates during the post-embryonic development of the tickOrnithodoros moubata
The ecdysteroid (ES) content of the soft tick Ornithodoros moubata was investigated during the five successive nymphal molting cycles by means of an enzyme immunoassay (EIA). Samples were submitted to esterase hydrolysis in order to release free ecdysteroids from the acyl-ester conjugates (AP = apolar products). Crude and hydrolysed extracts were then analyzed by EIA using two different antibodies, a monoclonal raised against 20-hydroxyecdysone (20E) and a polychlonal raised against ecdysone (E). With the crude extracts, each molting cycle was associated with an ES peak, occurring in the middle of the instar. 20E was preponderant during the first 2 nymph cycles, but the proportion of E and …
Antiapoptotic effect of calcitonin gene-related peptide on oxidative stress-induced injury in H9c2 cardiomyocytes via the RAMP1/CRLR complex.
Calcitonin gene-related peptide (CGRP) plays an important role in the mediation of protective effects observed in situations such as ischemic preconditioning in rat hearts. In this study, we investigated in H9c2 rat cardiomyoblasts if the protective effect of CGRP could be linked to an inhibitory effect on the apoptotic pathway. We also determined the specificity of observed effects by treatment with adrenomedullin (ADM) in stress conditions generated by 100 microM hydrogen peroxide. Using MTT assays, we demonstrate that a pretreatment with CGRP decreases by half the loss of cell viability induced by H(2)O(2). CGRP inhibits phosphatidylserine externalization, caspase 3 activation and DNA fr…