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Th17 cells and interleukin-17 increase with poor prognosis in patients with acute myeloid leukemia.

Han Y, Ye A, Bi L, Wu J, Yu K, Zhang S - Cancer Sci. (2014)

Bottom Line: Plasma levels of interleukin (IL)-17, IL-22, IL-23, IL-1β, IL-6, and transforming growth factor (TGF)-β1 were significantly increased in blood and bone marrow in AML patients compared with healthy donors.Patients with high Th17 cell frequency had poor prognosis, whereas patients with high Th1 cell frequency had prolonged survival.Combined analysis of Th1 and Th17 cell frequencies improved the ability to predict patient outcomes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

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Interleukin (IL)-17A promotes the proliferation of AML cells via IL-17 receptor (IL-17R). (a) Acute myeloid leukemia (AML) cell lines HL-60, U937, Dami, and primary AML cells isolated from AML patients (n = 23) were incubated with or without IL-17A (50 ng/mL) for 7 days and proliferation was assayed by MTT. Data are showed in proliferation in the presence of IL-17A compared with control and expressed as mean ± SEM representing at least three independent experiments. (b) The IL-17RA expression of AML cells was measured using anti-CD217 PE antibody (solid line) or mouse IgG1 PE antibody (dotted line) by flow cytometry. Representative histograms (left panel) and statistical data (right panel) were shown. (c) A correlation was observed between the IL-17RA expression and the IL-17A-inducing proliferation. (d) The effects of IL-17R on U937 and primary AML cell proliferation were determined by incubating the cells with IL-17A (50 ng/mL) in the presence or absence of anti-IL-17R antibody (3 μg/mL) for 7 days. (e) Western blotting showed the phosphorylation of Akt and Stat3 were significantly increased after IL-17A stimulation for 6 h and lasted for 24 h in IL-17R+ AML cells. Representatives and statistical data were shown for four independent experiments.
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fig04: Interleukin (IL)-17A promotes the proliferation of AML cells via IL-17 receptor (IL-17R). (a) Acute myeloid leukemia (AML) cell lines HL-60, U937, Dami, and primary AML cells isolated from AML patients (n = 23) were incubated with or without IL-17A (50 ng/mL) for 7 days and proliferation was assayed by MTT. Data are showed in proliferation in the presence of IL-17A compared with control and expressed as mean ± SEM representing at least three independent experiments. (b) The IL-17RA expression of AML cells was measured using anti-CD217 PE antibody (solid line) or mouse IgG1 PE antibody (dotted line) by flow cytometry. Representative histograms (left panel) and statistical data (right panel) were shown. (c) A correlation was observed between the IL-17RA expression and the IL-17A-inducing proliferation. (d) The effects of IL-17R on U937 and primary AML cell proliferation were determined by incubating the cells with IL-17A (50 ng/mL) in the presence or absence of anti-IL-17R antibody (3 μg/mL) for 7 days. (e) Western blotting showed the phosphorylation of Akt and Stat3 were significantly increased after IL-17A stimulation for 6 h and lasted for 24 h in IL-17R+ AML cells. Representatives and statistical data were shown for four independent experiments.

Mentions: After showing elevated existence of Th17 cells in BM from AML patients, we next investigated whether IL-17A, a signature cytokine secreted by Th17 cells, has any effects on AML cells. First, we assessed the proliferation of AML cells in the presence or absence of IL-17A. As shown in Figure 4(a), 50 ng/mL IL-17A only exhibited an increase in the proliferation of U937 as well as primary AML cells, but not in HL-60 and Dami cells. After treatment with IL-17A for 7 days, S phase cells of U937 and primary AML cells, although increased, were not statistically significant compared with control (P > 0.05, Fig. S1). IL-17A had also no significant effect on the induction of apoptosis (Fig. S2). IL-17R has been found to be ubiquitously expressed in many tissues and cell types.(25) We further investigated whether the IL-17R expression associates with IL-17-induced proliferation. Abundant expression of IL-17RA was present in U937 cells as well as most primary AML cells, but only weak expression in HL-60 and Dami cells (Fig. 4b), which was further confirmed by measuring the relative expression of IL-17R mRNA (Fig. S3). A positive correlation between IL-17A-induced proliferation and the IL-17RA expression was observed in primary AML cells (Fig. 4c). Therefore, we determined the role of IL-17R in IL-17A-induced AML cell proliferation using anti-IL-17R antibody. As shown in Figure 4(d), anti-IL-17R antibody significantly inhibited AML cell proliferation in the presence of IL-17A.


Th17 cells and interleukin-17 increase with poor prognosis in patients with acute myeloid leukemia.

Han Y, Ye A, Bi L, Wu J, Yu K, Zhang S - Cancer Sci. (2014)

Interleukin (IL)-17A promotes the proliferation of AML cells via IL-17 receptor (IL-17R). (a) Acute myeloid leukemia (AML) cell lines HL-60, U937, Dami, and primary AML cells isolated from AML patients (n = 23) were incubated with or without IL-17A (50 ng/mL) for 7 days and proliferation was assayed by MTT. Data are showed in proliferation in the presence of IL-17A compared with control and expressed as mean ± SEM representing at least three independent experiments. (b) The IL-17RA expression of AML cells was measured using anti-CD217 PE antibody (solid line) or mouse IgG1 PE antibody (dotted line) by flow cytometry. Representative histograms (left panel) and statistical data (right panel) were shown. (c) A correlation was observed between the IL-17RA expression and the IL-17A-inducing proliferation. (d) The effects of IL-17R on U937 and primary AML cell proliferation were determined by incubating the cells with IL-17A (50 ng/mL) in the presence or absence of anti-IL-17R antibody (3 μg/mL) for 7 days. (e) Western blotting showed the phosphorylation of Akt and Stat3 were significantly increased after IL-17A stimulation for 6 h and lasted for 24 h in IL-17R+ AML cells. Representatives and statistical data were shown for four independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
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fig04: Interleukin (IL)-17A promotes the proliferation of AML cells via IL-17 receptor (IL-17R). (a) Acute myeloid leukemia (AML) cell lines HL-60, U937, Dami, and primary AML cells isolated from AML patients (n = 23) were incubated with or without IL-17A (50 ng/mL) for 7 days and proliferation was assayed by MTT. Data are showed in proliferation in the presence of IL-17A compared with control and expressed as mean ± SEM representing at least three independent experiments. (b) The IL-17RA expression of AML cells was measured using anti-CD217 PE antibody (solid line) or mouse IgG1 PE antibody (dotted line) by flow cytometry. Representative histograms (left panel) and statistical data (right panel) were shown. (c) A correlation was observed between the IL-17RA expression and the IL-17A-inducing proliferation. (d) The effects of IL-17R on U937 and primary AML cell proliferation were determined by incubating the cells with IL-17A (50 ng/mL) in the presence or absence of anti-IL-17R antibody (3 μg/mL) for 7 days. (e) Western blotting showed the phosphorylation of Akt and Stat3 were significantly increased after IL-17A stimulation for 6 h and lasted for 24 h in IL-17R+ AML cells. Representatives and statistical data were shown for four independent experiments.
Mentions: After showing elevated existence of Th17 cells in BM from AML patients, we next investigated whether IL-17A, a signature cytokine secreted by Th17 cells, has any effects on AML cells. First, we assessed the proliferation of AML cells in the presence or absence of IL-17A. As shown in Figure 4(a), 50 ng/mL IL-17A only exhibited an increase in the proliferation of U937 as well as primary AML cells, but not in HL-60 and Dami cells. After treatment with IL-17A for 7 days, S phase cells of U937 and primary AML cells, although increased, were not statistically significant compared with control (P > 0.05, Fig. S1). IL-17A had also no significant effect on the induction of apoptosis (Fig. S2). IL-17R has been found to be ubiquitously expressed in many tissues and cell types.(25) We further investigated whether the IL-17R expression associates with IL-17-induced proliferation. Abundant expression of IL-17RA was present in U937 cells as well as most primary AML cells, but only weak expression in HL-60 and Dami cells (Fig. 4b), which was further confirmed by measuring the relative expression of IL-17R mRNA (Fig. S3). A positive correlation between IL-17A-induced proliferation and the IL-17RA expression was observed in primary AML cells (Fig. 4c). Therefore, we determined the role of IL-17R in IL-17A-induced AML cell proliferation using anti-IL-17R antibody. As shown in Figure 4(d), anti-IL-17R antibody significantly inhibited AML cell proliferation in the presence of IL-17A.

Bottom Line: Plasma levels of interleukin (IL)-17, IL-22, IL-23, IL-1β, IL-6, and transforming growth factor (TGF)-β1 were significantly increased in blood and bone marrow in AML patients compared with healthy donors.Patients with high Th17 cell frequency had poor prognosis, whereas patients with high Th1 cell frequency had prolonged survival.Combined analysis of Th1 and Th17 cell frequencies improved the ability to predict patient outcomes.

View Article: PubMed Central - PubMed

Affiliation: Laboratory of Internal Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Show MeSH
Related in: MedlinePlus