Interleukin (IL)‐17 promotes macrophages to produce IL‐8, IL‐6 and tumour necrosis factor‐α in aplastic anaemia

Gu, Yan; Hu, Xiaojing; Liu, Chuanfang; Qv, Xun; Xu, Cheng-Hui

doi:10.1111/j.1365-2141.2008.07161.x

Cited by 67 publications

(49 citation statements)

References 31 publications

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“…A previous study in humans showed elevated expression of IL-17A mRNA in BMMCs and PBMCs in 28 patients with severe AA before any specific therapy, 28 which is concordant with our findings. However, others found no difference in the frequencies and numbers of Th17 cells between patients with AA and healthy controls.…”

Section: Discussionsupporting

confidence: 93%

“…Indeed, IL-17 was not detectable in all but one study published to date in the plasma of patients with severe AA. 28,29,37 IL-17 might play a role directly at the site of BM destruction, as it is the case for other inflammatory cytokines. These cytokines were not detected either in the plasma of patients with AA in a very recent comprehensive cytokine analysis.…”

Section: Discussionmentioning

confidence: 99%

“…27 Because Th17-mediated immune responses have been reported in autoimmune disorders, we hypothesized that Th17 cells could contribute to the development of BM failure in mice, as in some AA patients. 28 However, a recent report showed a very limited role of Th17 cells in AA patients, 29 whereas other studies revealed reciprocal developmental pathways for the generation of pathogenic effector Th17 and Treg cells. 8,30 Here we examined the role of Th17 immune responses in AA by assessing Th17 and Treg cells in the presence in AA patients before and after immunosuppressive therapy and by testing the preventive/therapeutic effects of anti-IL-17 antibody in abrogating BM destruction in our mouse model.…”

Section: Introductionmentioning

confidence: 99%

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Th17 immune responses contribute to the pathophysiology of aplastic anemia

Latour

Visconte

Takaku

et al. 2010

Blood

163

139

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T helper type 17 (Th17) cells have been characterized based on production of interleukin-17 (IL-17) and association with autoimmune diseases. We studied the role of Th17 cells in aplastic anemia (AA) by isolating Th17 cells from patients blood (n ‫؍‬ 41) and bone marrow (BM) mononuclear cells (n ‫؍‬ 7). The frequency and total number of CD3 ؉ CD4 ؉ IL-17-producing T cells were increased in AA patients at presentation compared with healthy controls (P ‫؍‬ .0007 and .02, respectively) and IntroductionTh17 cells have been characterized recently in mice as a novel subset of CD4 ϩ T cells that produce interleukin-17A (IL-17A), IL-17-F, and IL-22, 1,2 and serve as immune effectors in various settings, including inflammation, infection, and autoimmunity. 3,4 Th17 cells produce a large amount of IL-17A, a cytokine that coordinates tissue inflammation by inducing the expression of proinflammatory cytokines (such as IL-6 and tumor necrosis factor [TNF]), chemokines (such as KC, MCP-1, and MIP-2), and matrix metalloproteases that mediate tissue infiltration and tissue destruction. 5 In mice, the differentiation program of Th17 cells from naive CD4 ϩ T cells requires the activation of the transcription factor, orphan nuclear receptor ROR␥t, 6 and the presence of IL-6 and transforming growth factor-␤ (TGF-␤). 7,8 In humans, Th17 differentiation is under the control of IL-1␤, 10 Several studies have reported the association of IL-17 with inflammatory disorders, such as rheumatoid arthritis, asthma, multiple sclerosis, and lupus, 11 as well as hematologic disorders, such as myelodysplastic syndrome 12,13 and acute myeloid leukemia. 14 Aplastic anemia (AA), a disease characterized by peripheral blood pancytopenia and bone marrow (BM) hypoplasia, 15 is an immunemediated disorder in most cases with active destruction of hematopoietic cells by effector T lymphocytes. 16 Recovery of autologous hematopoiesis in patients who failed to engraft after conditioning and stem cell transplantation, 17 and responsiveness of patients to immunosuppressive therapies, 18 provided powerful evidence for the pivotal role of the immune system in the disease pathophysiology. Immoderate production of interferon-␥ (IFN-␥), TNF-␣, and IL-2 from patients'T cells suggests that the hematopoietic cells are destroyed through a Th1 response, [19][20][21] as illustrated by the up-regulation of the transcription factor T-bet in patient T cells. 22 The description of nonrandom skewing of the V␤ chain families of the T-cell receptor in patient peripheral blood (PB) revealed that expanded oligoclonal or monoclonal specific V␤ subfamilies selectively induced apoptosis of hematopoietic progenitor cells. 23 Regulatory T cells (Tregs), which control and suppress autoreactive T cells, are decreased at disease presentation in almost all patients. 24 We have developed murine models for immune-mediated BM failure by the infusion of allogeneic lymph node (LN) cells into sublethally irradiated recipients for which treatment with limited number of Treg cells, 25 or anti-IFN...

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Th17 immune responses contribute to the pathophysiology of aplastic anemia

Latour

Visconte

Takaku

et al. 2010

Blood

163

139

View full text Add to dashboard Cite

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“…IL-17 has been reported to exhibit various effects on tumor progression. Certain studies have indicated that Th17 cells are involved in tissue inflammation via the induction of IL-8, IL-6, cyclooxygenase-2, matrix metalloproteinase (MMP)-1, MMP-3, CXCL1 and nitric oxide synthase-2 release by surrounding cells, such as fibroblasts, macrophages, endothelial and epithelial cells (46,47), which are involved in angiogenesis, tumor proliferation (48), invasion and metastasis (49,50). By contrast, other studies have reported Th17 cells exhibit an inhibitory influence on tumor growth (51,52).…”

Section: Discussionmentioning

confidence: 99%

Expression of Th1- Th2- and Th17-associated cytokines in laryngeal carcinoma

Wang

et al. 2016

Oncology Letters

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Abstract. T-helper (Th) 0 cell differentiation into Th1 or Th2 cells is dependent on a number of transcription factors that act at specific time points to regulate gene expression. Th17 cells, a subset of interleukin (IL)-17-producing T cells distinct from Th1 or Th2 cells, are considered to exhibit a critical function in inflammation and autoimmune diseases, as well as cancer development. In the present study, the expression of Th1-, Th2-and Th17-associated cytokines in laryngeal cancer and pericarcinoma tissues obtained from 57 laryngeal carcinoma patients was investigated. The association between Th1, Th2 and Th17 infiltration and tumor development was also evaluated. Reverse transcription-polymerase chain reaction and western blotting results revealed that the mRNA and protein expression of Th2 cytokines was lower, while the expression of Th1 and Th17 cytokines was higher in tumor tissues than in pericarcinoma tissues. Furthermore, the early stage cancer patients exhibited a higher level of interferon-γ, IL-2 and IL-17 mRNA expression than those at advanced stages. Cancer tissues exhibited higher Th17 cytokine expression than pericarcinoma tissues. By contrast, Th1 cytokine expression was increased in pericarcinoma tissues compared with cancer tissues. These results indicate that high expression of Th1-and Th17-associated cytokines in laryngeal carcinoma may contribute to suppression of cancer development and a relatively good prognosis.

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“…19,20 Because cytokines such as transforming growth factor-β, 37 interferon-γ, 37 tumor necrosis factor-α, 38,39 IL-6, 39 IL-17A, 39 and IL-1β 40,41 may be involved in the pathogenesis of aplastic anemia, we evaluated whether the addition of these cytokines may accelerate adipocyte differentiation. Unexpectedly, adipocyte differentiation was suppressed by these cytokines, except for IL-6 (Online Supplementary Figure S5A-F).…”

Section: Regulation Of Bm-msc Differentiation By Gata2mentioning

confidence: 99%

GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells

et al. 2014

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Methods Generation of bone marrow mesenchymal stem cellsTo generate mouse BM-MSC, bone marrow cells from GATA2 conditional knockout mice were cultured in MesenCult MSC Basal Medium supplemented with 20% MSC stimulatory supplements (Stem Cell Technologies). The BM-MSC were transfected with the retroviruses expressing iCre to delete the DNA binding domain of GATA2 by inducing the Cre-loxP system. 21,22 To generate human BM-MSC, bone marrow mononuclear cells from healthy donors were cultured with Dulbecco's modified Eagle's medium (Life Technologies) supplemented with 20% fetal bovine serum (Life Technologies), 10 ng/mL basic fibroblast growth factor (PeproTech), 10 mM HEPES (Life Technologies), and 100 μg/mL penicillin/streptomycin (Invitrogen). [23][24][25] Established BM-MSC were used until the seventh generation.The study was approved by the ethical committee of Tohoku University Graduate School of Medicine. Clinical samples were collected after obtaining written informed consent. The ethics policies of the Declaration of Helsinki were followed. Characterization of bone marrow mesenchymal stem cellsBM-MSC immunophenotypes were determined using a FACSAria II (BD). To induce differentiation into adipocytes, human Mesenchymal Stem Cell Adipogenic Differentiation Medium (Lonza) was used. After 12-16 days, morphological changes were assessed using an inverted microscope. Typical adipocytes were stained with Oil Red O.2 The area of mature adipocytes was determined using HistoQuest software (Novel Science). Quantitative reverse transcriptase polymerase chain reaction analysis and transcription profilingQuantitative reverse transcriptase polymerase chain reaction analysis (RT-PCR) was performed as previously described.26 Primer sequences are available upon request.For transcription profiling, the Human Genome U133 Plus 2.0 Array was used (Affymetrix). Gene ontology analysis was conducted using the DAVID bioinformatics program (http://david.abcc.ncifcrf.gov/). Short interfering RNA-mediated knockdownAnti-GATA2 and control short interfering RNA (siRNA) 26 were transfected into human BM-MSC with Lipofectamine TM RNAiMAX reagent (Life Technologies). Cells were analyzed 48 h after transfection. Viral vectors and cell transductionRetroviral overexpression of GATA2 was performed using the MSCV retrovirus vector, which co-expresses green fluorescent protein (GFP) by internal ribosome entry sites (IRES), transfecting into Platinum Retroviral Packaging Cell Lines (PLAT-F) 27 with FuGENE HD (Roche). Human BM-MSC were pretreated with Retronectin (TAKARA BIO.), and GFP-positive cells were sorted using FACSAria II (BD Biosciences).Co-culture of CD34-positive-enriched cells with a mesenchymal stem cell feeder layer BM-MSC were transfected with control or GATA2-siRNA. On day 3, control and GATA2 knockdowned BM-MSC, respectively, were replaced with serum-free medium containing CD34-positiveenriched cells (RIKEN). Serum-free medium (StemPro-34 SFM: Life Technologies) contained 100 ng/mL stem cell factor, 100 ng/mL interleukin (...

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Interleukin (IL)‐17 promotes macrophages to produce IL‐8, IL‐6 and tumour necrosis factor‐α in aplastic anaemia

Cited by 67 publications

References 31 publications

Th17 immune responses contribute to the pathophysiology of aplastic anemia

Th17 immune responses contribute to the pathophysiology of aplastic anemia

Expression of Th1- Th2- and Th17-associated cytokines in laryngeal carcinoma

GATA2 regulates differentiation of bone marrow-derived mesenchymal stem cells

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