Advertisement
JBC

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


     

Originally published In Press as doi:10.1074/jbc.M300430200 on January 27, 2003

J. Biol. Chem., Vol. 278, Issue 15, 12729-12736, April 11, 2003
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
278/15/12729    most recent
M300430200v1
Right arrow Submit a Letter to Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
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 arrowRequest Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, N.
Right arrow Articles by Oppenheim, J. J.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, N.
Right arrow Articles by Oppenheim, J. J.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Ca2+-independent Protein Kinase Cs Mediate Heterologous Desensitization of Leukocyte Chemokine Receptors by Opioid Receptors*

Ning ZhangDagger , Dave HodgeDagger , Thomas J. Rogers§, and Joost J. OppenheimDagger

From the Dagger  Laboratory of Molecular Immunoregulation, Intramural Research Support Program, Frederick, Maryland 21702-1201 and the § Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

Heterologous desensitization of chemokine receptors by opioids has been considered to contribute to their immunosuppressive effects. Previous studies show that Met-enkephalin, an endogenous opioid, down-regulates chemotaxis of selected chemokine receptors via phosphorylation. In the present study, we further investigated the molecular mechanism of such cross-regulation. Our data showed that preincubation with Met-enkephalin inhibited both MIP-1alpha -mediated chemotaxis and Ca2+ flux of monocytes in a dose-dependent manner. The inhibitory effects were maximal using nanomolar concentrations of activating chemokines, a concentration found in physiological conditions. A decrease both in chemokine receptor affinity and in coupling efficiency between receptors and G protein were observed, which directly contributed to the desensitization effects. However, comparing with chemokines such as MIP-1alpha and MCP-1, opioids did not elicit a calcium flux, failed to induce MIP-1alpha receptors internalization, and mediated a less potent heterologous desensitization. We hypothesized that these differences might originate from the involvement of different protein kinase C (PKC) isotypes. In our studies, opioid-mediated down-regulation of MIP-1alpha receptors could be blocked by the general PKC inhibitor calphostin C, but not by the calcium-dependent classic PKC inhibitor Go6976. Western blotting analysis and immunofluorescent staining further showed that only calcium-independent PKCs were activated upon opioid stimulation. Thus, opioids achieve desensitization of chemokine receptors via a unique pathway, involving only calcium-independent PKC isotypes.

* This work was supported in part by National Institutes of Health Research Grants DA-11130, DA-14230, DA-06550, and DA-13429.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Laboratory of Molecular Immunoregulation, Intramural Research Support Program, Bldg. 560, Rm. 21-89A, Frederick, MD 21702-1201.

Copyright © 2003 by The American Society for Biochemistry and Molecular Biology, Inc.
Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 J. Immunol.Home page
J. Grigat, A. Soruri, U. Forssmann, J. Riggert, and J. Zwirner
Chemoattraction of Macrophages, T Lymphocytes, and Mast Cells Is Evolutionarily Conserved within the Human {alpha}-Defensin Family
J. Immunol., September 15, 2007; 179(6): 3958 - 3965.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
N. Zhang, D. Yang, H. Dong, Q. Chen, D. I. Dimitrova, T. J. Rogers, M. Sitkovsky, and J. J. Oppenheim
Adenosine A2a receptors induce heterologous desensitization of chemokine receptors
Blood, July 1, 2006; 108(1): 38 - 44.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
C. A. Lunn, J. S. Fine, A. Rojas-Triana, J. V. Jackson, X. Fan, T. T. Kung, W. Gonsiorek, M. A. Schwarz, B. Lavey, J. A. Kozlowski, et al.
A Novel Cannabinoid Peripheral Cannabinoid Receptor-Selective Inverse Agonist Blocks Leukocyte Recruitment in Vivo
J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 780 - 788.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
N. Zhang and J. J. Oppenheim
Crosstalk between chemokines and neuronal receptors bridges immune and nervous systems
J. Leukoc. Biol., December 1, 2005; 78(6): 1210 - 1214.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
S. Ali, H. Robertson, J. H. Wain, J. D. Isaacs, G. Malik, and J. A. Kirby
A Non-Glycosaminoglycan-Binding Variant of CC Chemokine Ligand 7 (Monocyte Chemoattractant Protein-3) Antagonizes Chemokine-Mediated Inflammation
J. Immunol., July 15, 2005; 175(2): 1257 - 1266.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
M. W. Nasser, R. J. Marjoram, S. L. Brown, and R. M. Richardson
Cross-Desensitization among CXCR1, CXCR2, and CCR5: Role of Protein Kinase C-{epsilon}
J. Immunol., June 1, 2005; 174(11): 6927 - 6933.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
F.-S. Shie, R. M. Breyer, and T. J. Montine
Microglia Lacking E Prostanoid Receptor Subtype 2 Have Enhanced A{beta} Phagocytosis yet Lack A{beta}-Activated Neurotoxicity
Am. J. Pathol., April 1, 2005; 166(4): 1163 - 1172.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
N. Zhang, S. Inan, A. Cowan, R. Sun, J. M. Wang, T. J. Rogers, M. Caterina, and J. J. Oppenheim
A proinflammatory chemokine, CCL3, sensitizes the heat- and capsaicin-gated ion channel TRPV1
PNAS, March 22, 2005; 102(12): 4536 - 4541.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Res.Home page
R. Sun, P. Gao, L. Chen, D. Ma, J. Wang, J. J. Oppenheim, and N. Zhang
Protein Kinase C {zeta} Is Required for Epidermal Growth Factor-Induced Chemotaxis of Human Breast Cancer Cells
Cancer Res., February 15, 2005; 65(4): 1433 - 1441.
[Abstract] [Full Text] [PDF]

Home page
 Pharmacol. Rev.Home page
I. Tegeder and G. Geisslinger
Opioids As Modulators of Cell Death and Survival--Unraveling Mechanisms and Revealing New Indications
Pharmacol. Rev., September 1, 2004; 56(3): 351 - 369.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
A. V. Gulino, D. Moratto, S. Sozzani, P. Cavadini, K. Otero, L. Tassone, L. Imberti, S. Pirovano, L. D. Notarangelo, R. Soresina, et al.
Altered leukocyte response to CXCL12 in patients with warts hypogammaglobulinemia, infections, myelokathexis (WHIM) syndrome
Blood, July 15, 2004; 104(2): 444 - 452.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
R. Badolato
Leukocyte circulation: one-way or round-trip? Lessons from primary immunodeficiency patients
J. Leukoc. Biol., July 1, 2004; 76(1): 1 - 6.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
N. Zhang, T. J. Rogers, M. Caterina, and J. J. Oppenheim
Proinflammatory Chemokines, Such as C-C Chemokine Ligand 3, Desensitize {micro}-Opioid Receptors on Dorsal Root Ganglia Neurons
J. Immunol., July 1, 2004; 173(1): 594 - 599.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2003 by the American Society for Biochemistry and Molecular Biology.
Advertisement
spacer
Advertisement
Advertisement