Zileuton induces hemoglobin F synthesis in erythroid progenitors: role of the l-arginine–nitric oxide signaling pathway

Haynes, Johnson; Baliga, B S; Obiako, Boniface; Ofori-Acquah, Solomon F.; Pace, Betty S.

doi:10.1182/blood-2003-08-2969

Cited by 42 publications

(23 citation statements)

References 30 publications

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“…It is in accordance with results that l-arginine alone does not increase serum NOx production in steady-state patients, however it does when given together with hydroxyurea (Morris et al, 2003). Neither l-arginine alone nor l-arginine in combination with NOS inhibitor effected hydroxyurea-mediated induction of HbF synthesis in erythroid progenitors (Haynes et al, 2004). L-arginine did not change the suppression of burst forming unit-erythroid (BFU-E) colony growth and stimulation of HbF synthesis by hydroxyurea in erythroid progenitors (Baliga et al, 2010).…”

Section: No/cgmp Stimulation Of γ-Globin Gene Expressionsupporting

confidence: 90%

Nitric Oxide / Cyclic Nucleotide Regulation of Globin Genes in Erythropoiesis

Čokić¹,

Beleslin-Čokić²,

Jovčić³

et al. 2012

Hematology - Science and Practice

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Section: No/cgmp Stimulation Of γ-Globin Gene Expressionsupporting

confidence: 90%

Nitric Oxide / Cyclic Nucleotide Regulation of Globin Genes in Erythropoiesis

Čokić¹,

Beleslin-Čokić²,

Jovčić³

et al. 2012

Hematology - Science and Practice

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“…Antagonists of the LT pathway, such as LT receptor antagonists, or zileuton, which are currently licensed for asthma, 66 could be used to ameliorate inflammation and AH in SCD patients. It is pertinent to mention that zileuton is structurally similar to hydroxyurea, has been shown to increase hemoglobin F production in primary erythroid cells in vitro, 67 and may have clinical utility in the treatment of SCD.…”

Section: Discussionmentioning

confidence: 99%

Placenta growth factor induces 5-lipoxygenase–activating protein to increase leukotriene formation in sickle cell disease

Patel

Gonsalves

Yang

et al. 2009

Blood

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IntroductionInflammation is increasingly recognized as central to the pathophysiology of sickle cell disease (SCD) and is manifest as leukocytosis, elevated levels of inflammatory cytokines, and activation of neutrophils, monocytes, and endothelial cells. [1][2][3][4] It is present at steady state and is strongly associated with acute painful events, acute chest, and early mortality. 5,6 Current evidence strongly suggests that inflammation contributes to the endothelial cell dysfunction, potentiates vasoocclusion, and may also give rise to the airway hyperreactivity (AH) that often accompanies SCD. [7][8][9][10] Also intriguing is the spectrum of lung disease seen in this patient population, which spans from an increased incidence of AH and obstructive lung disease in children, [11][12][13] to restrictive lung disease and pulmonary vascular remodeling, which is associated with pulmonary hypertension in adults. [14][15][16][17][18] Leukotrienes (LT) mediate both inflammation and AH. 19-22 5-Lipoxygenase (5-LO) and its activating partner, 5-lipoxygenase activating protein (FLAP), catalyze the production of LT from arachidonic acid (AA) by generating 5-hydroperoxyeicostatraenoic acid (5-HPETE) and leukotriene A 4 (LTA 4 ). LTA 4 is the pivotal intermediate from which other LTs (ie, LTB 4 and cysteinyl LT [CysLT], LTC 4 , LTD 4 , and LTE 4 ) are formed. 20 LTB 4 is one of the most potent chemoattractant for neutrophils, eosinophils, and mediator of inflammation. CysLT, on the other hand, are potent bronchoconstrictors that play an important role in edema, inflammation, and mucus secretion in asthma and were previously termed "slow releasing substances." 23 LT play an important role in the pathogenesis of inflammatory disorders, specifically asthma, rheumatoid arthritis, and inflammatory bowel disease. [19][20][21] Studies by Bigby and coworkers 24,25 have shown that both tumor necrosis factor-␣ (TNF-␣) and lipopolysaccharide (LPS) induce the expression of FLAP in THP-1 cells. These studies showed the importance of nuclear factor-B (NF-B) and CCAAT/enhancer binding protein (C/EBP) transcription factors in the LPS-mediated FLAP expression. 24 LTB 4 levels are higher in SCD patients at steady state, which are further increased in vasoocclusive pain crises (VOC) and acute chest syndrome (ACS). 26 Very recently, increased LTE 4 has been observed in patients with SCD, which is associated with a higher incidence of pain. 27 However, less is understood about how LTs are increased in SCD at the molecular level.Placenta growth factor (PlGF) is an angiogenic growth factor with similar effects on endothelium as vascular endothelial growth factor (VEGF) and is primarily expressed by placental trophoblasts. [28][29][30] More recently, we and others show that erythroid cells, but not other hematopoietic cells, produce PlGF, and its expression is high in SCD and thalassemia. 31,32 VEGFR1 is its cognate receptor and is expressed on endothelial cells, alveolar epithelial cells, mast cells, and monocytes. We have previously shown that...

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“…by guest www.bloodjournal.org From primary human CD34 ϩ cells, and modified by hydroxyurea and butyrate therapy. [124][125][126][127][128] This signaling includes (1) modulation of soluble guanylate cyclase and of cyclic AMP and GMP 124,128 ; (2) increased nitric oxide production 126 ; (3) changes in protein kinases modulated by stem cell factor 127 ; and (4) inhibition of Stat3 phosphorylation. 125 New therapies to increase HbF levels in humans may result from exploiting these observations.…”

Section: Therapeutic Approaches To Reactivation Of ␥-Globin and Hbf Imentioning

confidence: 99%