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 Inoue, Y.
Right arrow Articles by Harada, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Inoue, Y.
Right arrow Articles by Harada, M.
The Journal of Immunology, 2004, 172: 2147-2154.
Copyright © 2004 by The American Association of Immunologists

Novel Regulatory Mechanisms of CD40-Induced Prostanoid Synthesis by IL-4 and IL-10 in Human Monocytes

Yasushi Inoue, Takeshi Otsuka1, Hiroaki Niiro, Shuji Nagano, Yojirou Arinobu, Eiichi Ogami, Mitsuteru Akahoshi, Katsuhisa Miyake, Ichiro Ninomiya, Sakiko Shimizu, Hitoshi Nakashima and Mine Harada

Department of Medicine and Biosystemic Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

Interleukins IL-4 and IL-10 are considered to be central regulators for the limitation and eventual termination of inflammatory responses in vivo, based on their potent anti-inflammatory effects toward LPS-stimulated monocytes/macrophages and neutrophils. However, their role in T cell-dependent inflammatory responses has not been fully elucidated. In this study, we investigated the effects of both cytokines on the production of PGE2, a key molecule of various inflammatory conditions, in CD40-stimulated human peripheral blood monocytes. CD40 ligation of monocytes induced the synthesis of a significant amount of PGE2 via inducible expression of the cyclooxygenase (COX)-2 gene. Both IL-10 and IL-4 significantly inhibited PGE2 production and COX-2 expression in CD40-stimulated monocytes. Using specific inhibitors for extracellular signal-related kinase (ERK) and p38 mitogen-activated protein kinase (MAPK), we found that both kinase pathways are involved in CD40-induced COX-2 expression. CD40 ligation also resulted in the activation of NF-{kappa}B. Additional experiments exhibited that CD40 clearly induced the activation of the upstream kinases MAPK/ERK kinase 1/2, MAPK kinase 3/6, and I-{kappa}B in monocytes. IL-10 significantly inhibited CD40-induced activation of the ERK, p38 MAPK, and NF-{kappa}B pathways; however, inhibition by IL-4 was limited to the ERK pathway in monocytes. Neither IL-10 nor IL-4 affected the recruitment of TNFR-associated factors 2 and 3 to CD40 in monocytes. Collectively, IL-10 and IL-4 use novel regulatory mechanisms for CD40-induced prostanoid synthesis in monocytes, thus suggesting a potential role for these cytokines in regulating T cell-induced inflammatory responses, including autoimmune diseases.




This article has been cited by other articles:


Home page
 BloodHome page
H.-J. Zhou, L. V. Pham, A. T. Tamayo, Y.-C. Lin-Lee, L. Fu, L. C. Yoshimura, and R. J. Ford
Nuclear CD40 interacts with c-Rel and enhances proliferation in aggressive B-cell lymphoma
Blood, September 15, 2007; 110(6): 2121 - 2127.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Leveille, M. Bouillon, W. Guo, J. Bolduc, E. Sharif-Askari, Y. El-Fakhry, C. Reyes-Moreno, R. Lapointe, Y. Merhi, J. A. Wilkins, et al.
CD40 Ligand Binds to {alpha}5beta1 Integrin and Triggers Cell Signaling
J. Biol. Chem., February 23, 2007; 282(8): 5143 - 5151.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
Y. Shibata, J. Gabbard, M. Yamashita, S. Tsuji, M. Smith, A. Nishiyama, R. A. Henriksen, and Q. N. Myrvik
Heat-killed BCG induces biphasic cyclooxygenase 2+ splenic macrophage formation--role of IL-10 and bone marrow precursors
J. Leukoc. Biol., September 1, 2006; 80(3): 590 - 598.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
Y.-C. Lin-Lee, L. V. Pham, A. T. Tamayo, L. Fu, H.-J. Zhou, L. C. Yoshimura, G. L. Decker, and R. J. Ford
Nuclear Localization in the Biology of the CD40 Receptor in Normal and Neoplastic Human B Lymphocytes
J. Biol. Chem., July 7, 2006; 281(27): 18878 - 18887.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
P. M.-C. Dang, C. Elbim, J.-C. Marie, M. Chiandotto, M.-A. Gougerot-Pocidalo, and J. El-Benna
Anti-inflammatory effect of interleukin-10 on human neutrophil respiratory burst involves inhibition of GM-CSF-induced p47PHOX phosphorylation through a decrease in ERK1/2 activity
FASEB J, July 1, 2006; 20(9): 1504 - 1506.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
P. K. A. Mongini, J. K. Inman, H. Han, R. J. Fattah, S. B. Abramson, and M. Attur
APRIL and BAFF Promote Increased Viability of Replicating Human B2 Cells via Mechanism Involving Cyclooxygenase 2.
J. Immunol., June 1, 2006; 176(11): 6736 - 6751.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
J. Koenigsknecht-Talboo and G. E. Landreth
Microglial Phagocytosis Induced by Fibrillar {beta}-Amyloid and IgGs Are Differentially Regulated by Proinflammatory Cytokines
J. Neurosci., September 7, 2005; 25(36): 8240 - 8249.
[Abstract] [Full Text] [PDF]

Home page
 J. Leukoc. Biol.Home page
Y. Shibata, A. Nishiyama, H. Ohata, J. Gabbard, Q. N. Myrvik, and R. A. Henriksen
Differential effects of IL-10 on prostaglandin H synthase-2 expression and prostaglandin E2 biosynthesis between spleen and bone marrow macrophages
J. Leukoc. Biol., April 1, 2005; 77(4): 544 - 551.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2004 by The American Association of Immunologists, Inc. All rights reserved.