Cutting edge: Activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia

Amit K. Verma, Dilip K. Deb, Antonella Sassano, Suman Kambhampati, Amittha Wickrema, Shahab Uddin, Mani Mohindru, Koen Van Besien, Leonidas C. Platanias

Research output: Contribution to journalArticle

83 Citations (Scopus)

Abstract

Myelosuppressive cytokines, in particular IFN-γ and TNF-α, play an important role in the pathogenesis of idiopathic aplastic anemia in humans. It is unknown whether these negative regulators of hemopoiesis suppress stem cells by activating a common signaling cascade or via distinct nonoverlapping pathways. In this study, we provide evidence that a common element in signaling for IFN-γ and TNF-α in human hemopoietic progenitors is the p38/MapKapK-2 signaling cascade. Our studies indicate that pharmacological inhibition of p38 reverses the suppressive effects of IFN-γ and TNF-α on normal human bone marrow-derived erythroid and myeloid progenitors. Most importantly, inhibition of p38 strongly enhances hemopoietic progenitor colony formation from aplastic anemia bone marrows in vitro. Thus, p38 appears to play a critical role in the pathogenesis of aplastic anemia, suggesting that selective pharmacological inhibitors of this kinase may prove useful in the treatment of aplastic anemia and other cytokine-mediated bone marrow failure syndromes.

Original languageEnglish (US)
Pages (from-to)5984-5988
Number of pages5
JournalJournal of Immunology
Volume168
Issue number12
StatePublished - Jun 15 2002
Externally publishedYes

Fingerprint

Aplastic Anemia
p38 Mitogen-Activated Protein Kinases
Cytokines
Bone Marrow
Pharmacology
Phosphotransferases
Stem Cells

ASJC Scopus subject areas

  • Immunology

Cite this

Cutting edge : Activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia. / Verma, Amit K.; Deb, Dilip K.; Sassano, Antonella; Kambhampati, Suman; Wickrema, Amittha; Uddin, Shahab; Mohindru, Mani; Van Besien, Koen; Platanias, Leonidas C.

In: Journal of Immunology, Vol. 168, No. 12, 15.06.2002, p. 5984-5988.

Research output: Contribution to journalArticle

Verma, AK, Deb, DK, Sassano, A, Kambhampati, S, Wickrema, A, Uddin, S, Mohindru, M, Van Besien, K & Platanias, LC 2002, 'Cutting edge: Activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia', Journal of Immunology, vol. 168, no. 12, pp. 5984-5988.
Verma, Amit K. ; Deb, Dilip K. ; Sassano, Antonella ; Kambhampati, Suman ; Wickrema, Amittha ; Uddin, Shahab ; Mohindru, Mani ; Van Besien, Koen ; Platanias, Leonidas C. / Cutting edge : Activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia. In: Journal of Immunology. 2002 ; Vol. 168, No. 12. pp. 5984-5988.
@article{bad6a8df54c54e33b64b0dd61287ffc4,
title = "Cutting edge: Activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia",
abstract = "Myelosuppressive cytokines, in particular IFN-γ and TNF-α, play an important role in the pathogenesis of idiopathic aplastic anemia in humans. It is unknown whether these negative regulators of hemopoiesis suppress stem cells by activating a common signaling cascade or via distinct nonoverlapping pathways. In this study, we provide evidence that a common element in signaling for IFN-γ and TNF-α in human hemopoietic progenitors is the p38/MapKapK-2 signaling cascade. Our studies indicate that pharmacological inhibition of p38 reverses the suppressive effects of IFN-γ and TNF-α on normal human bone marrow-derived erythroid and myeloid progenitors. Most importantly, inhibition of p38 strongly enhances hemopoietic progenitor colony formation from aplastic anemia bone marrows in vitro. Thus, p38 appears to play a critical role in the pathogenesis of aplastic anemia, suggesting that selective pharmacological inhibitors of this kinase may prove useful in the treatment of aplastic anemia and other cytokine-mediated bone marrow failure syndromes.",
author = "Verma, {Amit K.} and Deb, {Dilip K.} and Antonella Sassano and Suman Kambhampati and Amittha Wickrema and Shahab Uddin and Mani Mohindru and {Van Besien}, Koen and Platanias, {Leonidas C.}",
year = "2002",
month = "6",
day = "15",
language = "English (US)",
volume = "168",
pages = "5984--5988",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "12",

}

TY - JOUR

T1 - Cutting edge

T2 - Activation of the p38 mitogen-activated protein kinase signaling pathway mediates cytokine-induced hemopoietic suppression in aplastic anemia

AU - Verma, Amit K.

AU - Deb, Dilip K.

AU - Sassano, Antonella

AU - Kambhampati, Suman

AU - Wickrema, Amittha

AU - Uddin, Shahab

AU - Mohindru, Mani

AU - Van Besien, Koen

AU - Platanias, Leonidas C.

PY - 2002/6/15

Y1 - 2002/6/15

N2 - Myelosuppressive cytokines, in particular IFN-γ and TNF-α, play an important role in the pathogenesis of idiopathic aplastic anemia in humans. It is unknown whether these negative regulators of hemopoiesis suppress stem cells by activating a common signaling cascade or via distinct nonoverlapping pathways. In this study, we provide evidence that a common element in signaling for IFN-γ and TNF-α in human hemopoietic progenitors is the p38/MapKapK-2 signaling cascade. Our studies indicate that pharmacological inhibition of p38 reverses the suppressive effects of IFN-γ and TNF-α on normal human bone marrow-derived erythroid and myeloid progenitors. Most importantly, inhibition of p38 strongly enhances hemopoietic progenitor colony formation from aplastic anemia bone marrows in vitro. Thus, p38 appears to play a critical role in the pathogenesis of aplastic anemia, suggesting that selective pharmacological inhibitors of this kinase may prove useful in the treatment of aplastic anemia and other cytokine-mediated bone marrow failure syndromes.

AB - Myelosuppressive cytokines, in particular IFN-γ and TNF-α, play an important role in the pathogenesis of idiopathic aplastic anemia in humans. It is unknown whether these negative regulators of hemopoiesis suppress stem cells by activating a common signaling cascade or via distinct nonoverlapping pathways. In this study, we provide evidence that a common element in signaling for IFN-γ and TNF-α in human hemopoietic progenitors is the p38/MapKapK-2 signaling cascade. Our studies indicate that pharmacological inhibition of p38 reverses the suppressive effects of IFN-γ and TNF-α on normal human bone marrow-derived erythroid and myeloid progenitors. Most importantly, inhibition of p38 strongly enhances hemopoietic progenitor colony formation from aplastic anemia bone marrows in vitro. Thus, p38 appears to play a critical role in the pathogenesis of aplastic anemia, suggesting that selective pharmacological inhibitors of this kinase may prove useful in the treatment of aplastic anemia and other cytokine-mediated bone marrow failure syndromes.

UR - http://www.scopus.com/inward/record.url?scp=0037097528&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037097528&partnerID=8YFLogxK

M3 - Article

C2 - 12055203

AN - SCOPUS:0037097528

VL - 168

SP - 5984

EP - 5988

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 12

ER -