کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2542277 1122695 2006 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Roles of Ras and extracellular signal-regulated kinase-dependent IκBα degradation in oridonin-enhanced phagocytosis of apoptotic cells by human macrophage-like U937 cells
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ایمونولوژی
پیش نمایش صفحه اول مقاله
Roles of Ras and extracellular signal-regulated kinase-dependent IκBα degradation in oridonin-enhanced phagocytosis of apoptotic cells by human macrophage-like U937 cells
چکیده انگلیسی

Rapid recognition and ingestion of apoptotic cells by phagocytes are important for the prevention of toxic intracellular contents release, thereby attenuate inflammation and autoimmune diseases such as systemic lupus erythematosus (SLE). We have reported that oridonin isolated from Rabdosia rubescens enhanced phagocytosis of apoptotic U937 cells by macrophage-like U937 cells through TNFα and IL-1β release. In this study, the molecular mechanisms involved in this phagocytic process are investigated. Inhibitors of Ras and Raf1 kinase significantly reduced oridonin-induced phagocytic stimulation as well as extracellular signal-regulated kinase (ERK) phosphorylation. Simultaneously, oridonin-enhanced engulfment was partially blocked by a nuclear factor (NF)-κB inhibitor PDTC or proteasome inhibitor MG132. Further studies revealed that oridonin induced IκBα degradation, which was prevented by Ras inhibitor manumycin A, ERK inhibitor PD98059, but not prevented by c-Jun N-terminal kinase (JNK) MAPK inhibitor SP600125, and up-regulated expression of IL-1β precursor. These results demonstrate that Ras/Raf1/ERK signaling pathway-dependent IκBα degradation, resulting in NF-κB activation, participates in regulation of oridonin-enhanced phagocytosis, and one of its effector functions is to induce synthesis of IL-1β, which partially contribute to phagocytic activity of oridonin.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: International Immunopharmacology - Volume 6, Issue 2, February 2006, Pages 260–268
نویسندگان
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