title: IL-12 could induce monocytic tumor cells directional differentiation.
abstract: Interleukin-12 (IL-12), a member of interleukin family, plays a critical role in immune responses and anti-tumor activity. In this study, the effects of IL-12 on monocytic tumor cell lines differentiation to macrophagocyte and its likely mechanism was investigated. We examined the differentiation markers, morphological and functional changes, and possible mechanism in IL-12-treated THP-1 and U937 cells. It was found that IL-12 could up-regulated macrophage surface marker CD68 and CD11b expression in a time-dependent manner. Morphologically, after IL-12 treatment, THP-1 and U937 cells became round or irregular shape, even stretched many cell membrane protuberances; some cell nuclei became fuzzy or completely disappeared, and the chromatin appeared dense and cordlike. Furthermore, IL-12-induced monocytic tumor cell differentiation was accompanied by the growth arrest with G1-phase accumulation and S-phase reduction; apoptosis increased with anti-apoptosis protein Bcl-2 down-expression and pro-apoptosis protein Fas up-regulation, and enhanced phagocytosis function. The IL-12-induced macrophage differentiation of THP-1 and U937 cells was associated with the up-regulation of c-fms expression and the CSF-1R Tyr 809 site phosphorylation. These findings have revealed that IL-12 could induce monocytic tumor cells directional differentiation into macrophage-like cells, and its mechanism is possible connected with the up-regulation of c-fms expression and the phosphorylation of CSF-1R Tyr-809 site.
authors.affiliation: College of Laboratory Medicine, Key Laboratory of Laboratory Medical Diagnostics of Education Ministry, Chongqing Medical University, Chongqing, 400016, China.
authors.forename: Ting-Ting
authors.initials: TT
authors.lastname: Ma
authors.forename: Bi-Tao
authors.initials: BT
authors.lastname: Wu
authors.forename: Yan
authors.initials: Y
authors.lastname: Lin
authors.forename: Hai-Yu
authors.initials: HY
authors.lastname: Xiong
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.forename: Zi-Wei
authors.initials: ZW
authors.lastname: Li
authors.forename: Feng
authors.initials: F
authors.lastname: Cheng
authors.forename: Zhi-Guang
authors.initials: ZG
authors.lastname: Tu
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis; D002453:Cell Cycle; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D048430:Cell Shape; D004705:Endocytosis; D006801:Humans; D018664:Interleukin-12 / Q000502:physiology*; D008264:Macrophages / Q000502:physiology*; D010587:Phagocytosis; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000378:metabolism
chemical_list: D015703:Antigens, CD; D018664:Interleukin-12; D016186:Receptor, Macrophage Colony-Stimulating Factor