| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Medicine, Pulmonary and Critical Care Section, Yale University School of Medicine, New Haven, CT 06520
cAMP is an important second messenger with immunomodulatory
properties. Elevation of intracellular cAMP in T cells, induced by
agents such as IL-1
or PGs, inhibits T cell activation. In effector
T cells, an increase in the level of intracellular cAMP inhibits
cytokine production in Th1 cells but stimulates cytokine production in
Th2 cells. Here we report that cAMP-induced effects in Th2 cells occur
independently of the protein kinase A pathway, which is the major
mediator of cAMP-induced signaling events in most cell types. Instead,
cAMP stimulates activation of p38 mitogen-activated protein kinase in
Th2 cells. This appears to be a Th2-selective event because cAMP barely
increased p38 phosphorylation in Th1 cells. We show that in Th2 cells,
cAMP promotes the production of both IL-5 and IL-13, which play
distinct but critical roles in asthma pathogenesis. Our data also show
that cAMP causes increased phosphorylation of the transcription factor
GATA-3, which we have shown is a critical regulator of Th2 cytokine
gene expression and, in turn, of airway inflammation in mice. Thus,
Th2-specific GATA-3 expression and p38 mitogen-activated protein kinase
activation together provide a molecular basis for the differential
effects of cAMP in the two T helper cell
subsets.
This article has been cited by other articles:
|
|
 |
|
  A. C. Liberman, J. Druker, D. Refojo, F. Holsboer, and E. Arzt Glucocorticoids inhibit GATA-3 phosphorylation and activity in T cells FASEB J, May 1, 2009; 23(5): 1558 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. J. Scheinman and O. Avni Transcriptional Regulation of Gata3 in T Helper Cells by the Integrated Activities of Transcription Factors Downstream of the Interleukin-4 Receptor and T Cell Receptor J. Biol. Chem., January 30, 2009; 284(5): 3037 - 3048. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. L. Wurster and M. J. Pazin BRG1-Mediated Chromatin Remodeling Regulates Differentiation and Gene Expression of T Helper Cells Mol. Cell. Biol., December 15, 2008; 28(24): 7274 - 7285. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Klein-Hessling, T. Bopp, M. K. Jha, A. Schmidt, S. Miyatake, E. Schmitt, and E. Serfling Cyclic AMP-induced Chromatin Changes Support the NFATc-mediated Recruitment of GATA-3 to the Interleukin 5 Promoter J. Biol. Chem., November 7, 2008; 283(45): 31030 - 31037. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. S. Viger, S. M. Guittot, M. Anttonen, D. B. Wilson, and M. Heikinheimo Role of the GATA Family of Transcription Factors in Endocrine Development, Function, and Disease Mol. Endocrinol., April 1, 2008; 22(4): 781 - 798. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 C. Martucci, S. Franchi, D. Lattuada, A. E. Panerai, and P. Sacerdote Differential involvement of RelB in morphine-induced modulation of chemotaxis, NO, and cytokine production in murine macrophages and lymphocytes J. Leukoc. Biol., January 1, 2007; 81(1): 344 - 354. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Sarkar, S. Das, D. Chakroborty, U. R. Chowdhury, B. Basu, P. S. Dasgupta, and S. Basu Cutting Edge: Stimulation of Dopamine D4 Receptors Induce T Cell Quiescence by Up-Regulating Kruppel-Like Factor-2 Expression through Inhibition of ERK1/ERK2 Phosphorylation J. Immunol., December 1, 2006; 177(11): 7525 - 7529. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. Sun, J. Hong, Y. C. Q. Zang, X. Liu, and J. Z. Zhang Altered expression of vasoactive intestinal peptide receptors in T lymphocytes and aberrant Th1 immunity in multiple sclerosis Int. Immunol., December 1, 2006; 18(12): 1691 - 1700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. B. Cismasiu, S. Ghanta, J. Duque, D. I. Albu, H.-M. Chen, R. Kasturi, and D. Avram BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes Blood, October 15, 2006; 108(8): 2695 - 2702. [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]
|
|
|
|
 |
|
 J. Rubenfeld, J. Guo, N. Sookrung, R. Chen, W. Chaicumpa, V. Casolaro, Y. Zhao, V. Natarajan, and S. Georas Lysophosphatidic acid enhances interleukin-13 gene expression and promoter activity in T cells Am J Physiol Lung Cell Mol Physiol, January 1, 2006; 290(1): L66 - L74. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Roy, J. Wang, R. Charboneau, H. H. Loh, and R. A. Barke Morphine Induces CD4+ T Cell IL-4 Expression through an Adenylyl Cyclase Mechanism Independent of the Protein Kinase A Pathway J. Immunol., November 15, 2005; 175(10): 6361 - 6367. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. S. Sundrud, S. E. VanCompernolle, K. A. Eger, T. C. Bruno, A. Subramaniam, S. Mummidi, S. K. Ahuja, and D. Unutmaz Transcription factor GATA-1 potently represses the expression of the HIV-1 coreceptor CCR5 in human T cells and dendritic cells Blood, November 15, 2005; 106(10): 3440 - 3448. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. F. Bouchard, H. Taniguchi, and R. S. Viger Protein Kinase A-Dependent Synergism between GATA Factors and the Nuclear Receptor, Liver Receptor Homolog-1, Regulates Human Aromatase (CYP19) PII Promoter Activity in Breast Cancer Cells Endocrinology, November 1, 2005; 146(11): 4905 - 4916. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Yamashita, R. Shinnakasu, H. Asou, M. Kimura, A. Hasegawa, K. Hashimoto, N. Hatano, M. Ogata, and T. Nakayama Ras-ERK MAPK Cascade Regulates GATA3 Stability and Th2 Differentiation through Ubiquitin-Proteasome Pathway J. Biol. Chem., August 19, 2005; 280(33): 29409 - 29419. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y.-L. Yu, Y.-J. Chiang, Y.-C. Chen, M. Papetti, C.-G. Juo, A. I. Skoultchi, and J. J. Y. Yen MAPK-mediated Phosphorylation of GATA-1 Promotes Bcl-XL Expression and Cell Survival J. Biol. Chem., August 19, 2005; 280(33): 29533 - 29542. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C.-H. Woo, J.-H. Lim, and J.-H. Kim VCAM-1 upregulation via PKC{delta}-p38 kinase-linked cascade mediates the TNF-{alpha}-induced leukocyte adhesion and emigration in the lung airway epithelium Am J Physiol Lung Cell Mol Physiol, February 1, 2005; 288(2): L307 - L316. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Nishihara, M. Hwang, S. Kizaka-Kondoh, L. Eckmann, and P. A. Insel Cyclic AMP Promotes cAMP-responsive Element-binding Protein-dependent Induction of Cellular Inhibitor of Apoptosis Protein-2 and Suppresses Apoptosis of Colon Cancer Cells through ERK1/2 and p38 MAPK J. Biol. Chem., June 18, 2004; 279(25): 26176 - 26183. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Romani, F. Bistoni, R. Gaziano, S. Bozza, C. Montagnoli, K. Perruccio, L. Pitzurra, S. Bellocchio, A. Velardi, G. Rasi, et al. Thymosin {alpha} 1 activates dendritic cells for antifungal Th1 resistance through Toll-like receptor signaling Blood, June 1, 2004; 103(11): 4232 - 4239. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Tokoyoda, K. Tsujikawa, H. Matsushita, Y. Ono, T. Hayashi, Y. Harada, R. Abe, M. Kubo, and H. Yamamoto Up-regulation of IL-4 production by the activated cAMP/cAMP-dependent protein kinase (protein kinase A) pathway in CD3/CD28-stimulated naive T cells Int. Immunol., May 1, 2004; 16(5): 643 - 653. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. M. Masci, M. Galgani, S. Cassano, S. De Simone, A. Gallo, V. De Rosa, S. Zappacosta, and L. Racioppi HIV-1 gp120 induces anergy in naive T lymphocytes through CD4-independent protein kinase-A-mediated signaling J. Leukoc. Biol., December 1, 2003; 74(6): 1117 - 1124. [Abstract] [Full Text]
|
|
|
|
|
|
E. C. Lavelle, E. McNeela, M. E. Armstrong, O. Leavy, S. C. Higgins, and K. H. G. Mills Cholera Toxin Promotes the Induction of Regulatory T Cells Specific for Bystander Antigens by Modulating Dendritic Cell Activation J. Immunol., September 1, 2003; 171(5): 2384 - 2392. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.A. Wuyts, B.M. Vanaudenaerde, L.J. Dupont, M.G. Demedts, and G.M. Verleden Modulation by cAMP of IL-1{beta}-induced eotaxin and MCP-1 expression and release in human airway smooth muscle cells Eur. Respir. J., August 1, 2003; 22(2): 220 - 226. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-H. Chen, C. Seguin-Devaux, N. A. Burke, T. B. Oriss, S. C. Watkins, N. Clipstone, and A. Ray Transforming Growth Factor {beta} Blocks Tec Kinase Phosphorylation, Ca2+ Influx, and NFATc Translocation Causing Inhibition of T Cell Differentiation J. Exp. Med., June 16, 2003; 197(12): 1689 - 1699. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. J. Tremblay and R. S. Viger Transcription Factor GATA-4 Is Activated by Phosphorylation of Serine 261 via the cAMP/Protein Kinase A Signaling Pathway in Gonadal Cells J. Biol. Chem., June 6, 2003; 278(24): 22128 - 22135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Yoshino, Y. Osuga, Y. Hirota, K. Koga, T. Hirata, T. Yano, T. Ayabe, O. Tsutsumi, and Y. Taketani Endometrial Stromal Cells Undergoing Decidualization Down-Regulate Their Properties to Produce Proinflammatory Cytokines in Response to Interleukin-1{beta} via Reduced p38 Mitogen-Activated Protein Kinase Phosphorylation J. Clin. Endocrinol. Metab., May 1, 2003; 88(5): 2236 - 2241. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K.-Y. Hung, J.-W. Huang, C.-T. Chen, P.-H. Lee, and T.-J. Tsai Pentoxifylline modulates intracellular signalling of TGF-{beta} in cultured human peritoneal mesothelial cells: implications for prevention of encapsulating peritoneal sclerosis Nephrol. Dial. Transplant., April 1, 2003; 18(4): 670 - 676. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Klein-Hessling, M. K. Jha, B. Santner-Nanan, F. Berberich-Siebelt, T. Baumruker, A. Schimpl, and E. Serfling Protein Kinase A Regulates GATA-3-Dependent Activation of IL-5 Gene Expression in Th2 Cells J. Immunol., March 15, 2003; 170(6): 2956 - 2961. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Abe, K. Hasegawa, H. Wada, T. Morimoto, T. Yanazume, T. Kawamura, M. Hirai, Y. Furukawa, and T. Kita GATA-6 Is Involved in PPAR{gamma}-Mediated Activation of Differentiated Phenotype in Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2003; 23(3): 404 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Grader-Beck, A. A. F. L. van Puijenbroek, L. M. Nadler, and V. A. Boussiotis cAMP inhibits both Ras and Rap1 activation in primary human T lymphocytes, but only Ras inhibition correlates with blockade of cell cycle progression Blood, February 1, 2003; 101(3): 998 - 1006. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. K. Brint, K. A. Fitzgerald, P. Smith, A. J. Coyle, J.-C. Gutierrez-Ramos, P. G. Fallon, and L. A. J. O'Neill Characterization of Signaling Pathways Activated by the Interleukin 1 (IL-1) Receptor Homologue T1/ST2. A ROLE FOR JUN N-TERMINAL KINASE IN IL-4 INDUCTION J. Biol. Chem., December 13, 2002; 277(51): 49205 - 49211. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. F. Schwenger, C. C. Kok, E. Arthaningtyas, M. A. Thomas, C. J. Sanderson, and V. A. Mordvinov Specific Activation of Human Interleukin-5 Depends on de Novo Synthesis of an AP-1 Complex J. Biol. Chem., November 27, 2002; 277(49): 47022 - 47027. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Suarez, L. Mozo, and C. Gutierrez Generation of CD4+CD45RA+ Effector T Cells by Stimulation in the Presence of Cyclic Adenosine 5'-Monophosphate- Elevating Agents J. Immunol., August 1, 2002; 169(3): 1159 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hofer, H. Nathansen, M. Lohning, A. Radbruch, and R. Heinrich GATA-3 transcriptional imprinting in Th2 lymphocytes: A mathematical model PNAS, July 9, 2002; 99(14): 9364 - 9368. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Kerkela, S. Pikkarainen, T. Majalahti-Palviainen, H. Tokola, and H. Ruskoaho Distinct Roles of Mitogen-activated Protein Kinase Pathways in GATA-4 Transcription Factor-mediated Regulation of B-type Natriuretic Peptide Gene J. Biol. Chem., April 12, 2002; 277(16): 13752 - 13760. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Yin, C. Chen, S. J. Szabo, L. H. Glimcher, A. Ray, and J. Craft T-Bet Expression and Failure of GATA-3 Cross-Regulation Lead to Default Production of IFN-{gamma} by {gamma}{delta} T Cells J. Immunol., February 15, 2002; 168(4): 1566 - 1571. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Smits, E. C. de Jong, J. H. N. Schuitemaker, T. B. H. Geijtenbeek, Y. van Kooyk, M. L. Kapsenberg, and E. A. Wierenga Intercellular Adhesion Molecule-1/LFA-1 Ligation Favors Human Th1 Development J. Immunol., February 15, 2002; 168(4): 1710 - 1716. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
