| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
*
Clinical Research Center for Allergy and Rheumatology, National Sagamihara Hospital, Sagamihara, Kanagawa, Japan; and
Department of Medicine and Physical Therapy, Faculty of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan
Involvement of p38 mitogen-activated protein (MAP) kinase in human
T cell cytokine synthesis was investigated. p38 MAP kinase was clearly
induced in human Th cells activated through the TCR. SB203580, a highly
selective inhibitor of p38 MAP kinase, inhibited the induction of p38
MAP kinase in human Th cells. Major T cell cytokines, IL-2, IL-4, IL-5,
and IFN-
, were produced by Der f 2-specific Th clones upon
stimulation through the TCR. IL-5 synthesis alone was significantly
inhibited by SB203580 in a dose-dependent manner, whereas the
production of IL-2, IL-4, and IFN- was not affected. The
proliferation of activated T cells was not affected. IL-5 synthesis of
human Th clones induced upon stimulation with rIL-2, phorbol ester plus
anti-CD28 mAb, and immobilized anti-CD3 mAb plus soluble
anti-CD28 mAb was also suppressed by SB203580 in the same
concentration response relationship. The results clearly indicated that
IL-5 synthesis by human Th cells is dependent on p38 MAP kinase
activity, and is regulated distinctly from IL-2, IL-4, and IFN-
synthesis. Selective control of IL-5 synthesis will provide a novel
treatment devoid of generalized immune suppression for bronchial asthma
and atopic dermatitis that are characterized by eosinophilic
inflammation.
This article has been cited by other articles:
|
|
 |
|
  K. Maneechotesuwan, Y. Xin, K. Ito, E. Jazrawi, K.-Y. Lee, O. S. Usmani, P. J. Barnes, and I. M. Adcock Regulation of Th2 Cytokine Genes by p38 MAPK-Mediated Phosphorylation of GATA-3 J. Immunol., February 15, 2007; 178(4): 2491 - 2498. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Kogkopoulou, E. Tzakos, G. Mavrothalassitis, C. T. Baldari, F. Paliogianni, H. A. Young, and G. Thyphronitis Conditional up-regulation of IL-2 production by p38 MAPK inactivation is mediated by increased Erk1/2 activity J. Leukoc. Biol., May 1, 2006; 79(5): 1052 - 1060. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, M. F. Shannon, and I. G. Young A role for Ets1, synergizing with AP-1 and GATA-3 in the regulation of IL-5 transcription in mouse Th2 lymphocytes Int. Immunol., February 1, 2006; 18(2): 313 - 323. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 Y. Takanami-Ohnishi, S. Amano, S. Kimura, S. Asada, A. Utani, M. Maruyama, H. Osada, H. Tsunoda, Y. Irukayama-Tomobe, K. Goto, et al. Essential Role of p38 Mitogen-activated Protein Kinase in Contact Hypersensitivity J. Biol. Chem., September 27, 2002; 277(40): 37896 - 37903. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T ten Hove, B van den Blink, I Pronk, P Drillenburg, M P Peppelenbosch, and S J H van Deventer Dichotomal role of inhibition of p38 MAPK with SB 203580 in experimental colitis Gut, April 1, 2002; 50(4): 507 - 512. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Reimold, J. Kim, R. Finberg, and L. H. Glimcher Decreased immediate inflammatory gene induction in activating transcription factor-2 mutant mice Int. Immunol., February 1, 2001; 13(2): 241 - 248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Cannons, Y. Choi, and T. H. Watts Role of TNF Receptor-Associated Factor 2 and p38 Mitogen-Activated Protein Kinase Activation During 4-1BB-Dependent Immune Response J. Immunol., December 1, 2000; 165(11): 6193 - 6204. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
