کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2542309 1122697 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fludarabine induces pro-inflammatory activation of human monocytic cells through a MAPK/ERK pathway
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Fludarabine induces pro-inflammatory activation of human monocytic cells through a MAPK/ERK pathway
چکیده انگلیسی

Fludarabine is a nucleoside analogue that has been successfully employed for the treatment of low-grade lymphoid malignancies and, more recently, in nonmyeloablative preparative regimens for stem cell transplantation, due to its strong cytotoxic activity on lymphocytes. In this paper, we show that fludarabine can also induce pro-inflammatory stimulation of monocytic cells, as evaluated by increased expression of ICAM-1 and IL-8 release. To study the mechanisms involved, we employed selective inhibitors of MAPK and NF-κB pathways, both of which have been implicated in the modulation of ICAM-1 and IL-8. Our results showed that fludarabine effects were mediated through the activation of ERK and were independent on p38, JNK or NF-κB pathways. By Western blotting analysis we corroborated that fludarabine induced a rapid activation of ERK that was sustained for at least 30 min. Moreover, pro-inflammatory activation of monocytic cells by fludarabine was largely attenuated by coadministration of the free radical scavenger N-acetylcysteine suggesting the involvement of reactive oxygen species in fludarabine effects. Finally, we showed that fludarabine induced the activation of the transcription factor AP-1 not only in monocytic cells but also in non-proliferating lymphocytes from chronic lymphocytic leukemia. It is possible that some of fludarabine side effects in vivo may be attributed to cell activation/differentiation rather than induction of apoptosis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 6, Issue 5, May 2006, Pages 715–723
نویسندگان
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