2011
DOI: 10.1159/000329903
|View full text |Cite
|
Sign up to set email alerts
|

Cytokine-Induced Apoptosis of Beta-Thalassemia/Hemoglobin E Erythroid Progenitor Cells via Nitric Oxide-Mediated Process in vitro

Abstract: Background/Aim: β-Thalassemia/hemoglobin E (β-thal/HbE) is a common hereditary anemia in Thailand. Ineffective erythropoiesis due to apoptosis and decreased lifespan of circulating thalassemic red blood cells are the major causes of anemia. Changes to bone marrow microenvironment could contribute to apoptotic events. This study examined the effects of cytokines interleukin-1β, tumor necrosis factor-α and interferon-γ on apoptosis of β-thal/HbE erythroid progenitor cells in vitro, including nitric oxide-mediate… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
3
1
1

Citation Types

1
11
0

Year Published

2012
2012
2023
2023

Publication Types

Select...
9

Relationship

3
6

Authors

Journals

citations
Cited by 13 publications
(12 citation statements)
references
References 43 publications
1
11
0
Order By: Relevance
“…IL-1β propagates inflammation through various mechanisms, including perturbation of chemokine and cytokine signaling networks, responses that lead to the expansion and recruitment of neutrophils to several organs. This cytokine also promotes anemia owing to its negative effects on erythroid progenitors and erythropoietin signaling as well as alteration of the expression of ferritin and ferroportin [ 35 – 38 ]. Accordingly, NOMID mice produced higher levels of IL-1β in bone marrow compared to WT counterparts ( Fig 3A and S1 Data ), a response that correlated with excessive GSDMD processing in vivo in bone marrow, though the cleaved fragment was barely detected in this compartment ( S1B Fig ).…”
Section: Resultsmentioning
confidence: 99%
“…IL-1β propagates inflammation through various mechanisms, including perturbation of chemokine and cytokine signaling networks, responses that lead to the expansion and recruitment of neutrophils to several organs. This cytokine also promotes anemia owing to its negative effects on erythroid progenitors and erythropoietin signaling as well as alteration of the expression of ferritin and ferroportin [ 35 – 38 ]. Accordingly, NOMID mice produced higher levels of IL-1β in bone marrow compared to WT counterparts ( Fig 3A and S1 Data ), a response that correlated with excessive GSDMD processing in vivo in bone marrow, though the cleaved fragment was barely detected in this compartment ( S1B Fig ).…”
Section: Resultsmentioning
confidence: 99%
“…Although the center of the epiphysis in developing bones is normally hypoxic 33 , our results show that hypoxia is exacerbated in mutant limbs by the excessive amounts of IL-1β, which cause severe anemia of inflammation. Accordingly, chronic exposures to IL-1β are known to cause anemia through multiple mechanisms 38 , including attenuation of proliferation and differentiation of erythroid progenitors 39 , inhibition of erythropoietin production and signaling 40 , promotion of the biosynthesis of ferritin and down regulation of the expression of ferroportin 41, 42 , which enable the storage and the release of iron, respectively, by cells such as macrophages and hepatocytes. The specific mechanisms of anemia in NOMID mice are unclear, but this anomaly is associated with inflammation, and diminished expression of HIF-1α and its target genes, events that are associated with chondrocyte death.…”
Section: Discussionmentioning
confidence: 99%
“…Acetylcholine-induced vasodilation was impaired in ß-thalassemic mice despite eNOS overexpression, suggesting endothelial dysfunction and eNOS uncoupling [ 34 ]. However, the elevated blood nitrite found in our study could be explained by multiple factors, including ingestion of nitrite/nitrate-rich diet [ 36 ], inability of HbE to efficiently convert nitrite to NO compared to HbA [ 13 ], increased inducible NO synthase (iNOS) expression [ 37 ], and medications that enhance eNOS activity. Our study was limited by lack of diet control.…”
Section: Discussionmentioning
confidence: 99%