title: Autophagy enhanced phagocytosis of apoptotic cells by oridonin-treated human histocytic lymphoma U937 cells.
abstract: Macrophages rapidly engulf and remove apoptotic cells to limit the release of noxious cellular contents and to restrict autoimmune disease or inflammation. Recent developments reveal an important role in autophagy for clearance of apoptotic corpses. However, the relationship between autophagy and phagocytosis remains unclear. In this study we found that low doses of oridonin, an active diterpenoid, enhanced phagocytosis of apoptotic cells by human macrophage-like U937 cells, meanwhile it also induced autophagy in these U937 cells. Moreover, inhibition of extracellular signal-related kinase (ERK), nuclear factor-κB (NF-κB) and caspase-1 significantly suppressed oridonin-induced phagocytosis and autophagy. In addition, oridonin increased the protein levels of p-ERK, NF-κB, caspase-1 and pro IL-1β. Autophagic inhibitor 3-methyladenine (3-MA) decreased phagocytosis and the expression of ERK whereas increased the expression of NF-κB- and caspase-1-mediated IL-1β release. Beclin-1 (known as autophagic regulator) loss also led to the similar results. Pretreatment with autophagic agonist rapamycin caused opposite results. Autophagy-associated proteins, Beclin-1, LC3 and Atg4B, involved in this phagocytosis process. These results demonstrated that autophagy enhanced oridonin-induced phagocytosis through feedback regulation of ERK, NF-κB- and caspase-1-mediated IL-1β release.
authors.affiliation: China-Japan Research Institute of Medical Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang, PR China.
authors.forename: Linghe
authors.initials: L
authors.lastname: Zang
authors.forename: Qian
authors.initials: Q
authors.lastname: Xu
authors.forename: Yuanchao
authors.initials: Y
authors.lastname: Ye
authors.forename: Xin
authors.initials: X
authors.lastname: Li
authors.forename: Yanqiu
authors.initials: Y
authors.lastname: Liu
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Tashiro
authors.forename: Satoshi
authors.initials: S
authors.lastname: Onodera
authors.forename: Takashi
authors.initials: T
authors.lastname: Ikejima
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D020170:Caspase 1 / Q000378:metabolism; D045786:Diterpenes, Kaurane / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D025461:Feedback, Physiological / Q000187:drug effects; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D016328:NF-kappa B / Q000378:metabolism; D020298:U937 Cells
chemical_list: D045786:Diterpenes, Kaurane; D053583:Interleukin-1beta; D016328:NF-kappa B; C011959:oridonin; D048049:Extracellular Signal-Regulated MAP Kinases; D020170:Caspase 1