The JI
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Adachi, T.
Right arrow Articles by Alam, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Adachi, T.
Right arrow Articles by Alam, R.
The Journal of Immunology, 00, 165: 2198-2204.
Copyright © 00 by The American Association of Immunologists

The Differential Role of Extracellular Signal-Regulated Kinases and p38 Mitogen-Activated Protein Kinase in Eosinophil Functions1

Tetsuya Adachi, Barun K. Choudhury, Susan Stafford, Sanjiv Sur and Rafeul Alam2

Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Medical Branch, Galveston, TX 77555

The activation of eosinophils by cytokines is a major event in the pathogenesis of allergic diseases. We have investigated the activation of mitogen-activated protein (MAP) kinases and their functional relevance in eosinophil differentiation, survival, degranulation, and cytokine production. IL-5 induced phosphorylation and activation of extracellular signal-regulated kinases (ERK) and p38 MAP kinases in eosinophils. PD98059, a MAP/ERK kinase inhibitor, blocked phosphorylation of ERK1/2 in a dose-dependent manner. SB202190, a p38 inhibitor, blocked p38-dependent phosphorylation of activating transcription factor-2. To study the importance of the MAP kinases on eosinophil differentiation, we cultured mouse bone marrow cells with IL-3 and IL-5 in the presence of the inhibitors. SB202190 dramatically inhibited eosinophil differentiation by 71%. PD98059 was less potent and reduced eosinophil differentiation by 28%. Both inhibitors marginally inhibited eosinophil survival only at the highest doses. Prolonged incubation of eosinophils with IL-5 induced significant eosinophil-derived neurotoxin release. Both PD98059 and SB202190 nearly completely inhibited (87% and 100% inhibition, respectively) IL-5-stimulated eosinophil-derived neurotoxin release in a dose-dependent manner. Next, we examined the effect of the MAP kinase inhibitors on eosinophil production of the cytokine macrophage-inflammatory protein (MIP)-1{alpha}. PD98059 blocked C5a- but not ionomycin-induced MIP-1{alpha} production (59% inhibition at 50 µM concentration). In contrast, SB202190 nearly completely inhibited (99%) C5a-induced MIP-1{alpha} production. Further, it blocked ionomycin-stimulated production by 66%. Our results suggest that both p38 and ERK1/2 MAP kinases play an important role in eosinophil differentiation, cytokine production, and degranulation. The p38 MAP kinase plays a greater role than ERK1/2 in eosinophil differentiation and cytokine production.




This article has been cited by other articles:


Home page
 J. Immunol.Home page
T. Adachi, S. Hanaka, T. Masuda, H. Yoshihara, H. Nagase, and K. Ohta
Transduction of Phosphatase and Tensin Homolog Deleted on Chromosome 10 into Eosinophils Attenuates Survival, Chemotaxis, and Airway Inflammation
J. Immunol., December 15, 2007; 179(12): 8105 - 8111.
[Abstract] [Full Text] [PDF]

Home page
 Antimicrob. Agents Chemother.Home page
S. Wei, B. J. Daniel, M. J. Brumlik, M. E. Burow, W. Zou, I. A. Khan, S. Wadsworth, J. Siekierka, and T. J. Curiel
Drugs Designed To Inhibit Human p38 Mitogen-Activated Protein Kinase Activation Treat Toxoplasma gondii and Encephalitozoon cuniculi Infection
Antimicrob. Agents Chemother., December 1, 2007; 51(12): 4324 - 4328.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
J. H. Kang, D. H. Lee, H. Seo, J. S. Park, K. H. Nam, S. Y. Shin, C.-S. Park, and I. Y. Chung
Regulation of Functional Phenotypes of Cord Blood Derived Eosinophils by {gamma}-Secretase Inhibitor
Am. J. Respir. Cell Mol. Biol., November 1, 2007; 37(5): 571 - 577.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. M. Gorska, O. Cen, Q. Liang, S. J. Stafford, and R. Alam
Differential Regulation of Interleukin 5-stimulated Signaling Pathways by Dynamin
J. Biol. Chem., May 19, 2006; 281(20): 14429 - 14439.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
D. A. Sawatzky, D. A. Willoughby, P. R. Colville-Nash, and A. G. Rossi
The Involvement of the Apoptosis-Modulating Proteins ERK 1/2, Bcl-xL and Bax in the Resolution of Acute Inflammation in Vivo
Am. J. Pathol., January 1, 2006; 168(1): 33 - 41.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Crit. Care Med.Home page
W. Duan, J. H. P. Chan, K. McKay, J. R. Crosby, H. H. Choo, B. P. Leung, J. G. Karras, and W. S. F. Wong
Inhaled p38{alpha} Mitogen-activated Protein Kinase Antisense Oligonucleotide Attenuates Asthma in Mice
Am. J. Respir. Crit. Care Med., March 15, 2005; 171(6): 571 - 578.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Respir. Cell Mol. Bio.Home page
C. Taube, J. A. Nick, B. Siegmund, C. Duez, K. Takeda, Y.-H. Rha, J.-W. Park, A. Joetham, K. Poch, A. Dakhama, et al.
Inhibition of Early Airway Neutrophilia Does Not Affect Development of Airway Hyperresponsiveness
Am. J. Respir. Cell Mol. Biol., June 1, 2004; 30(6): 837 - 843.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Esnault and J. S. Malter
Hyaluronic Acid or TNF-{alpha} Plus Fibronectin Triggers Granulocyte Macrophage-Colony-Stimulating Factor mRNA Stabilization in Eosinophils Yet Engages Differential Intracellular Pathways and mRNA Binding Proteins
J. Immunol., December 15, 2003; 171(12): 6780 - 6787.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. Triggiani, F. Granata, B. Balestrieri, A. Petraroli, G. Scalia, L. Del Vecchio, and G. Marone
Secretory Phospholipases A2 Activate Selective Functions in Human Eosinophils
J. Immunol., March 15, 2003; 170(6): 3279 - 3288.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Apati, J. Janossy, A. Brozik, P. I. Bauer, and M. Magocsi
Calcium Induces Cell Survival and Proliferation through the Activation of the MAPK Pathway in a Human Hormone-dependent Leukemia Cell Line, TF-1
J. Biol. Chem., March 7, 2003; 278(11): 9235 - 9243.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
N. Sakai, T. Wada, K. Furuichi, Y. Iwata, K. Yoshimoto, K. Kitagawa, S. Kokubo, M. Kobayashi, S.-i. Takeda, H. Kida, et al.
p38 MAPK phosphorylation and NF-{kappa}B activation in human crescentic glomerulonephritis
Nephrol. Dial. Transplant., June 1, 2002; 17(6): 998 - 1004.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
S. Esnault and J. S. Malter
Extracellular signal-regulated kinase mediates granulocyte-macrophage colony-stimulating factor messenger RNA stabilization in tumor necrosis factor-alpha plus fibronectin-activated peripheral blood eosinophils
Blood, May 13, 2002; 99(11): 4048 - 4052.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Stafford, C. Lowell, S. Sur, and R. Alam
Lyn Tyrosine Kinase Is Important for IL-5-Stimulated Eosinophil Differentiation
J. Immunol., February 15, 2002; 168(4): 1978 - 1983.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2000 by The American Association of Immunologists, Inc. All rights reserved.