Inhibition of human erythroid colony‐forming units by interleukin‐1 is mediated by gamma interferon

Means, Robert T.; Dessypris, Emmanuel N.; Krantz, Sanford B.

doi:10.1002/jcp.1041500109

Cited by 135 publications

(68 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Another such finding involves the inconsistent in vitro effects of inflammatory cytokines associated with ACDI. Specifically, IFN-γ and TNF-α have been found to exert either negative or positive influences on erythropoiesis, depending on study conditions (29,30,46). In our culture conditions, the effects of IFN-γ on erythropoiesis show a strong dependency on iron availability.…”

Section: Methodsmentioning

confidence: 77%

“…The relevance of these findings to ACDI is suggested by prior implication of IFN-γ in erythropoietic repression in human chronic kidney disease and in multiple animal models of anemia (22,27,28). In addition, IFN-signaling pathways are known to participate in erythroid inhibition by TNF-α and IL-1 and in human idiopathic refractory anemia (29,30). In the rat arthritis model of ACDI, increased serum IFN-γ and decreased serum iron were observed (Supplemental Table 2).…”

Section: Ic Treatment Corrects Anemia and Erythropoietic Defects In Rmentioning

confidence: 99%

See 1 more Smart Citation

Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response

Richardson¹,

Delehanty²,

Bullock³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

The unique sensitivity of early red cell progenitors to iron deprivation, known as the erythroid iron restriction response, serves as a basis for human anemias globally. This response impairs erythropoietin-driven erythropoiesis and underlies erythropoietic repression in iron deficiency anemia. Mechanistically, the erythroid iron restriction response results from inactivation of aconitase enzymes and can be suppressed by providing the aconitase product isocitrate. Recent studies have implicated the erythroid iron restriction response in anemia of chronic disease and inflammation (ACDI), offering new therapeutic avenues for a major clinical problem; however, inflammatory signals may also directly repress erythropoiesis in ACDI. Here, we show that suppression of the erythroid iron restriction response by isocitrate administration corrected anemia and erythropoietic defects in rats with ACDI. In vitro studies demonstrated that erythroid repression by inflammatory signaling is potently modulated by the erythroid iron restriction response in a kinase-dependent pathway involving induction of the erythroid-inhibitory transcription factor PU.1. These results reveal the integration of iron and inflammatory inputs in a therapeutically tractable erythropoietic regulatory circuit.

show abstract

Section: Methodsmentioning

confidence: 77%

Section: Ic Treatment Corrects Anemia and Erythropoietic Defects In Rmentioning

confidence: 99%

Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response

Richardson¹,

Delehanty²,

Bullock³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

show abstract

“…[11][12][13] Interferon (IFN)-γ and tumor necrosis factor (TNF)-α, produced during the acute phase of malaria infection, have been considered as candidates for this suppressive factor because of their ability to inhibit the growth of erythroid colony-forming cells. [14][15][16] Other pro-inflammatory cytokines such as interleukin (IL)-12 and macrophage migration inhibitory factor have also been implicated in the pathogenesis of malarial anemia. 17 However, there is no conclusive evidence supporting a role for these cytokines in suppressed erythropoiesis during malaria infection.…”

Section: Introductionmentioning

confidence: 99%

STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia

Thawani¹,

Tam²,

Stevenson³

2008

Haematologica

View full text Add to dashboard Cite

The online version of this article contains a supplementary appendix. BackgroundThe contribution of pro-inflammatory cytokines to the pathogenesis of malarial anemia has been studied extensively but the roles of Th2 cytokines remain unknown. Here, we investigated the role of signal transducer and activator of transcription (STAT)6-mediated responses in erythropoietic suppression during acute malaria infection in mice. Design and MethodsNaïve and/or erythropoietin-treated wild-type and STAT6 -/-mice were infected with Plasmodium chabaudi AS (P. chabaudi), and the effects on parasitemia, hematologic parameters, erythropoietin receptor, TER119, and CD71 expression, in vitro erythropoietin-stimulated proliferation of splenic erythroid precursors, and serum cytokine levels were analyzed. To explore the role of interleukin-4 in STAT6-dependent erythropoietic suppression, mice were treated in vivo with a monoclonal antibody to interleukin-4 and the effects on parasitemia, hematologic parameters, and cytokine levels were analyzed. Results Infected STAT6-/-mice developed enhanced reticulocytosis compared to wild-type mice despite higher parasitemia and a similar course of anemia. Enhanced reticulocytosis in infected STAT6 -/-mice was associated with an increased frequency of late-stage erythroblasts, fewer leukocytes expressing CD71, and increased erythropoietin-stimulated proliferation of splenocytes compared to infected wild-type mice. Interleukin-4-depleted wildtype mice had increased levels of parasitemia and a course of reticulocytosis similar to responses observed in infected STAT6 -/-mice. Determination of serum cytokine levels in STAT6 -/-and wild-type mice depleted of interleukin-4 by treatment with mAb revealed significantly lower levels of interferon-γ compared to control wild-type mice during infection. ConclusionsTogether, these findings provide evidence for a STAT6-dependent mechanism in mediating erythropoietic suppression during acute blood-stage malaria and indicate a role for interleukin-4 and possibly interferon-γ in STAT6-induced erythropoietic suppression.Key words: malaria, anemia, erythropoiesis, STAT6, interleukin-4, interferon-γ.Citation: Thawani N, Tam M, and Stevenson MM. STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia. Haematologica 2009; 94:195-204. doi:10.3324/haematol.13422 ©2009 Ferrata Storti Foundation. This is an open-access paper. STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia ABSTRACT© F e r r a t a S t o r t i F o u n d a t i o n N. Thawani et al.

show abstract

“…9 Macrophage derived IL-1 has found to indirectly suppressed the erythropoiesis in vivo and in vitro by the help of tumor necrosis factor (TNF), and the IFN-γ. 10,11,12 Moreover, TNF shares many biological activities with interleukin-1. 13 In β-thalassemic patients, the increased number of activated macrophages have been observed, which is the main source of many pro-apoptotic cytokines, especially IL-1.…”

Section: Pagementioning

confidence: 99%

Interleukin-1 involved in Apoptosis of Beta-Thalassemia/Hemoglobin E Erythroid Progenitor Cells

2013

View full text Add to dashboard Cite

Objective:The major pathophysiological features of β-thalassemia are anemia and ineffective erythropoiesis. Ineffective erythropoiesis has been shown by an intense marrow erythroid hyperplasia and increased apoptosis during basophilic to orthochromatic normoblast stages. Some cytokines like interferon-γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin-1 (IL-1) have been found to involved in apoptosis. Although the pro-apoptotic activity of IFN-γ and TNF-α is well documented, there are only few studies on IL-1, especially on erythroid lineage. In this in vitro study, the role of cytokine IL-1α and IL-1β in apoptosis of erythroid progenitor cells from β-thalassemia/HbE patients was assessed.Methods: Erythroid progenitor cells were isolated from peripheral blood of healthy subjects and β-thalassemia/HbE patients. Cells were then cultured, with and without 20 ng/ml IL-1α and IL-1β. Total cells and percent cell viability were performed by using trypan blue staining. Percent cell apoptosis was analyzed by using flow cytometer.Results: Both IL-1α and IL-1 β were significantly decreased erythroid progenitor cells. IL-1 at 20 ng/ml reduced the glycophorin A positive cells and percent cell viability of erythroid progenitor cells from β-thalassemia/HbE patients, while there was increased apoptosis in this group. The highest percent apoptosis was observed in 20 ng/ml IL-1β treated β-thalassemia/HbE erythroid progenitor cells. Conclusion:IL-1β could be involved in apoptosis of erythroid progenitor cells from β-thalassemia/HbE patients which might be related with ineffective erythropoiesis of the disease. Key words: Ineffective erythropoiesis, apoptosis, IL-1, β-thalassemia/HbE ABSTRACT C O R R E S P O N D E N C E :Dr. Dalina I. A s i a n J ou r n al of Me d i ca l S c i e n ce , V o l um e -3 ( 2 0 1 2 ) h t

show abstract

Inhibition of human erythroid colony‐forming units by interleukin‐1 is mediated by gamma interferon

Cited by 135 publications

References 22 publications

Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response

Isocitrate ameliorates anemia by suppressing the erythroid iron restriction response

STAT6-mediated suppression of erythropoiesis in an experimental model of malarial anemia

Interleukin-1 involved in Apoptosis of Beta-Thalassemia/Hemoglobin E Erythroid Progenitor Cells

Contact Info

Product

Resources

About