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721.
722.
Coral García-Pastor Rafael Blázquez-Serra Ricardo J. Bosch Francisco J. Lucio Cazaña Ana B. Fernández-Martínez 《生物化学与生物物理学报:疾病的分子基础》2019,1865(9):2504-2515
The therapeutic efficacy of the antineoplastic drug cisplatin is limited by its nephrotoxicity, which affects particularly to proximal tubular cells (PTC). Cisplatin-induced cytotoxicity appears to be multifactorial and involves inflammation, oxidative stress as well as apoptosis. We have recently shown that the cyclo-oxygenase-2 (COX-2)/intracellular prostaglandin E2 (iPGE2)/EP receptor pathway mediates the apoptotic effect of cisplatin on human proximal tubular HK-2 cells. Here, we studied the effects on HK-2 cells of apoptotic bodies (ABs) generated after treatment of HK-2 cells with cisplatin. We found that ABs inhibited cell growth, induced apoptosis and increased COX-2 expression and iPGE2 in ABs-recipient HK-2 cells. Inhibition of the COX-2/iPGE2/EP receptor pathway in these cells prevented the effects of ABs without interfering with their internalization. Interestingly, 2nd generation ABs (i.e. ABs released by cells undergoing apoptosis upon treatment with ABs) did not trigger apoptosis in naïve HK-2 cells, and stimulated cell proliferation through the COX-2/iPGE2/EP receptor pathway. These results suggest that ABs, through iPGE2-dependent mechanisms, might have a relevant role in the natural history of cisplatin-induced acute kidney failure because they contribute first to the propagation of the noxious effects of cisplatin to non-injured PTC and then to the promotion of the proliferative tubular response required for proximal tubule repair. Since iPGE2 also mediates both cisplatin-induced HK-2 cell apoptosis, intervention in the COX-2/iPGE2/EP receptor pathway might provide us with new therapeutic avenues in patients with cisplatin-induced acute kidney injury. 相似文献
723.
724.
Natural and therapeutically-induced antibodies to cytokines 总被引:1,自引:0,他引:1
Roberto P. Revoltella 《Biotherapy》1998,10(4):321-331
Serum samples obtained from non-immunocompromised patients treated therapeutically with recombinant cytokines (e.g. Il-1α; Il-1β; Il-2 to Il-18; IFNα; GM-CSF; G-CSF; etc.) often reveal the presence of high affinity anti-cytokine antibodies. Antibody Fab binding in a saturable
manner by ELISA and RIA or western immunoblotting prove their specificity. Antibody level often increases in these patients
with repeated cytokine administration, suggesting boosts of antigen stimulation. However, the appearance in circulation of
auto-antibodies to exogenous cytokine is not always associated with a decreased clinical response to therapy. The demonstration
that non-neutralizing auto-antibodies to several natural cytokines can be found even in sera of normal healthy individuals
never treated before with cytokines and particularly during the last trimester of pregnancy and in cord-blood, suggests that
these naturally- occurring and therapeutically-induced auto-antibodies may exert different functions, not only as inhibitors
or antagonists but also as benificial physiological cytokine carriers or regulators of their activity. 相似文献