کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2167336 1092324 2011 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Stimulation of Fas (CD95) induces production of pro-inflammatory mediators through ERK/JNK-dependent activation of NF-κB in THP-1 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیولوژی سلول
پیش نمایش صفحه اول مقاله
Stimulation of Fas (CD95) induces production of pro-inflammatory mediators through ERK/JNK-dependent activation of NF-κB in THP-1 cells
چکیده انگلیسی

Although Fas is known to be an apoptosis triggering molecule, accumulating studies indicate that Fas has non-apoptotic functions in certain cases. In an effort to identify the role of Fas in macrophage function, the human macrophage-like cell line THP-1 was analyzed after treatment with agonistic anti-Fas monoclonal antibody or co-incubation with FasL-expressing cells. Stimulation of Fas induced the expression of pro-inflammatory mediators such as matrix metalloproteinase (MMP)-9 and IL-8. The specificity of the reaction was confirmed by the transfection of Fas-specific siRNAs which resulted in a suppression of Fas expression as well as the responsiveness to the agonistic antibody. Utilization of various signaling inhibitors and ELISA-based NF-κB DNA binding assay demonstrated that the signaling initiated from Fas is mediated by mitogen activated protein kinases (MAPKs) including extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) which induce subsequent activation of NF-κB. Furthermore, mixed cell culture experiment demonstrated that Fas can be activated through interaction with membrane-bound form of FasL during cell-to-cell interaction. These data indicate that Fas plays a role as an activation inducing molecule through interaction with its counterpart and Fas-mediate events are mediated by ERK/JNK MAPKs which subsequently activate NF-κB for the transcriptional activation of pro-inflammatory mediators.


► The function of Fas in inflammation was analyzed using a macrophage cell line THP-1.
► THP-1 cells were stimulated with agents that trigger Fas activation.
► Fas induced inflammatory mediators through activation of ERK, JNK and NF-κB.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Cellular Immunology - Volume 271, Issue 1, 2011, Pages 157–162
نویسندگان
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