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Calf Spleen Extractive Injection protects mice against cyclophosphamide-induced hematopoietic injury through G-CSF-mediated JAK2/STAT3 signaling.

ABSTRACT: Calf Spleen Extractive Injection (CSEI), extracted from the spleen of healthy cows (within 24?hours of birth), is a small-peptide-enriched extraction and often used as an ancillary agent in cancer therapy. This study evaluated the hematopoietic function of CSEI and its underlying mechanisms, principally in CHRF, K562 cells, BMNCs and a mouse model of cyclophosphamide (CTX)-induced hematopoietic suppression. CSEI promoted the proliferation and differentiation of CHRF and K562 cells, activated hematopoietic- and proliferation-related factors RSK1p90, ELK1 and c-Myc, and facilitated the expression of differentiation- and maturation-related transcription factors GATA-1, GATA-2. In the mice with hematopoietic suppression, 3 weeks of CSEI administration enhanced the bodyweights and thymus indices, suppressed the spleen indices and strongly elevated the production of HSPCs, neutrophils and B cells in bone marrow, ameliorated bone marrow cellularity, and regulated the ratio of peripheral blood cells. Proteome profiling combined with ELISA revealed that CSEI regulated the levels of cytokines, especially G-CSF and its related factors, in the spleen and plasma. Additional data revealed that CSEI promoted phosphorylation of STAT3, which was stimulated by G-CSF in both mice spleen and cultured BMNCs. Taken together, CSEI has the potential to improve hematopoietic function via the G-CSF-mediated JAK2/STAT3 signaling pathway.

SUBMITTER: Lu W

PROVIDER: S-EPMC5566473 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Calf Spleen Extractive Injection protects mice against cyclophosphamide-induced hematopoietic injury through G-CSF-mediated JAK2/STAT3 signaling.

Lu Wenqian W Jia Dongxu D An Shengshu S Mu Ming M Qiao Xinan X Liu Yan Y Li Xin X Wang Di D

Scientific reports 20170821 1

Calf Spleen Extractive Injection (CSEI), extracted from the spleen of healthy cows (within 24 hours of birth), is a small-peptide-enriched extraction and often used as an ancillary agent in cancer therapy. This study evaluated the hematopoietic function of CSEI and its underlying mechanisms, principally in CHRF, K562 cells, BMNCs and a mouse model of cyclophosphamide (CTX)-induced hematopoietic suppression. CSEI promoted the proliferation and differentiation of CHRF and K562 cells, activated hem ...[more]

PMID: 28827748

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Project description:ObjectivesAstragaloside IV (AS-IV), the main active component of Astragalus membranaceus, bears anti-inflammatory, antioxidant, and neuroprotective activity. Parkinson's disease (PD) is a common neurodegenerative disease. This study explored the protective effect of AS-IV on the cell model of PD.Materials and methodsSH-SY5Y cells were incubated with different concentrations (10, 50, 100, 150, and 200 μM) of 6-hydroxydopamine (6-OHDA) for 0, 3, 6, 12, 24, and 48 h to establish the PD cell model. Different concentrations (0, 25, 50, 100, 150, and 200 μM) of AS-IV or 15 mM JAK2/STAT3 pathway inhibitor SC99 was added for intervention 2 h before 6-OHDA treatment. The viability and morphological damage of 6-OHDA-treated SH-SY5Y cells were measured using MTT assay and Hoechst 33258 staining. The expression of microtubule associated protein 2 (MAP2) was detected by immunofluorescence staining. The levels of inflammation and oxidative stress were measured using ELISA. Apoptosis of 6-OHDA-treated SH-SY5Y cells was detected using flow cytometry, and phosphorylation level of JAK2 and STAT3 were detected using Western blot analysis.ResultsThe survival rate of SH-SY5Y cells treated with 100 μM 6-OHDA for 24 h was about 50%. AS-IV (25-100 μM) significantly improved the viability (all p < 0.01), increased MAP2 expression, and repaired the morphological damage induced by 6-OHDA. AS-IV inhibited IL-1β, IL-6, and TNF-α level (all p < 0.05), reduced MDA and ROS content and increased SOD concentration, thereby reducing inflammation and oxidative stress (all p < 0.01) in 6-OHDA-treated SH-SY5Y cells. Moreover, AS-IV decreased apoptosis rate and Bax/Bcl-2 ratio induced by 6-OHDA (all p < 0.05). Mechanically, AS-IV significantly increased the phosphorylation of JAK2 and STAT3 (p < 0.01); the addition of SC99 decreased the cell viability, increased the apoptosis rate, enhanced the levels of inflammatory factors and oxidative stress.ConclusionAS-IV enhanced the cell viability, and inhibited apoptosis, inflammation and oxidative stress of 6-OHDA-treated SH-SY5Y cells via activating the JAK2/STAT3 signaling pathway. This study may confer novel insights for the management of PD.

Dataset Information

Calf Spleen Extractive Injection protects mice against cyclophosphamide-induced hematopoietic injury through G-CSF-mediated JAK2/STAT3 signaling.

Publications

Calf Spleen Extractive Injection protects mice against cyclophosphamide-induced hematopoietic injury through G-CSF-mediated JAK2/STAT3 signaling.

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