JBC PeproTech; Our Business is Cytokines!

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


     

Originally published In Press as doi:10.1074/jbc.M203885200 on August 20, 2002

J. Biol. Chem., Vol. 277, Issue 43, 40594-40601, October 25, 2002
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
277/43/40594    most recent
M203885200v1
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 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 arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Kim, O. S.
Right arrow Articles by Jou, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kim, O. S.
Right arrow Articles by Jou, I.
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?

JAK-STAT Signaling Mediates Gangliosides-induced Inflammatory Responses in Brain Microglial Cells*

Ohn Soon KimDagger , Eun Jung ParkDagger , Eun-hye Joe, and Ilo Jou§

From the Department of Pharmacology, School of Medicine, Ajou University, Suwon 442-721, Korea

Neuronal cell membranes are particularly rich in gangliosides, which play important roles in brain physiology and pathology. Previously, we reported that gangliosides could act as microglial activators and are thus likely to participate in many neuronal diseases. In the present study we provide evidence that JAK-STAT inflammatory signaling mediates gangliosides-stimulated microglial activation. Both in rat primary microglia and murine BV2 microglial cells, gangliosides stimulated nuclear factor binding to GAS/ISRE elements, which are known to be STAT-binding sites. Consistent with this, gangliosides rapidly activated JAK1 and JAK2 and induced phosphorylation of STAT1 and STAT3. In addition, gangliosides increased transcription of the inflammation-associated genes inducible nitric-oxide syn- thase, ICAM-1, and MCP-1, which are reported to contain STAT-binding elements in their promoter regions. AG490, a JAK inhibitor, reduced induction of these genes, nuclear factor binding activity, and activation of STAT1 and -3 in gangliosides-treated microglia. AG490 also inhibited gangliosides-induced release of nitric oxide, an inflammation hallmark. Furthermore, AG490 markedly reduced activation of ERK1/2 MAPK, indicating that ERKs act downstream of JAK-STAT signaling during microglial activation. However, AG490 did not affect activation of p38 MAPK. We also report that the sialic acid residues present on gangliosides may be one of the essential components in activation of JAK-STAT signaling. The present study indicates that JAK-STAT signaling is an early event in gangliosides-induced brain inflammatory responses.

* This work was supported by Grant R01-2000-00164 from the Basic Research Program of the KOSEF and by Critical Technology 21[01-J-LF-B-77 Grant from the Korea Ministry of Science and Technology (to I. J.).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.

Dagger Both authors contributed equally to this paper.

§ To whom correspondence should be addressed: Dept. of Pharmacology, School of Medicine, Ajou University, Suwon, 442-721, Korea. Tel.: 82-31-219-5061; Fax: 82-31-219-5069; E-mail: jouilo@madang.ajou.ac. kr.

Copyright © 2002 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
H. J. Yoon, S.-B. Jeon, I.-H. Kim, and E. J. Park
Regulation of TLR2 Expression by Prostaglandins in Brain Glia
J. Immunol., June 15, 2008; 180(12): 8400 - 8409.
[Abstract] [Full Text] [PDF]

Home page
 Nephrol Dial TransplantHome page
N. Yang, M. Luo, R. Li, Y. Huang, R. Zhang, Q. Wu, F. Wang, Y. Li, and X. Yu
Blockage of JAK/STAT signalling attenuates renal ischaemia-reperfusion injury in rats
Nephrol. Dial. Transplant., January 1, 2008; 23(1): 91 - 100.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
I. Jou, J. H. Lee, S. Y. Park, H. J. Yoon, E.-H. Joe, and E. J. Park
Gangliosides Trigger Inflammatory Responses via TLR4 in Brain Glia
Am. J. Pathol., May 1, 2006; 168(5): 1619 - 1630.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
H. Y. Kim, S. J. Park, E.-h. Joe, and I. Jou
Raft-mediated Src Homology 2 Domain-containing Proteintyrosine Phosphatase 2 (SHP-2) Regulation in Microglia
J. Biol. Chem., April 28, 2006; 281(17): 11872 - 11878.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Cell Physiol.Home page
Y. Kuwano, T. Kawahara, H. Yamamoto, S. Teshima-Kondo, K. Tominaga, K. Masuda, K. Kishi, K. Morita, and K. Rokutan
Interferon-{gamma} activates transcription of NADPH oxidase 1 gene and upregulates production of superoxide anion by human large intestinal epithelial cells
Am J Physiol Cell Physiol, February 1, 2006; 290(2): C433 - C443.
[Abstract] [Full Text] [PDF]

Home page
 BloodHome page
R. Sano, A. Tessitore, A. Ingrassia, and A. d'Azzo
Chemokine-induced recruitment of genetically modified bone marrow cells into the CNS of GM1-gangliosidosis mice corrects neuronal pathology
Blood, October 1, 2005; 106(7): 2259 - 2268.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. Yadav, A. Kalita, S. Dhillon, and K. Banerjee
JAK/STAT3 Pathway Is Involved in Survival of Neurons in Response to Insulin-like Growth Factor and Negatively Regulated by Suppressor of Cytokine Signaling-3
J. Biol. Chem., September 9, 2005; 280(36): 31830 - 31840.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
S. Giri, N. Nath, B. Smith, B. Viollet, A. K. Singh, and I. Singh
5-Aminoimidazole-4-Carboxamide-1-{beta}-4-Ribofuranoside Inhibits Proinflammatory Response in Glial Cells: A Possible Role of AMP-Activated Protein Kinase
J. Neurosci., January 14, 2004; 24(2): 479 - 487.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Lee, S. Cha, M.-S. Lee, G. J. Cho, W. S. Choi, and K. Suk
Role of Antiproliferative B Cell Translocation Gene-1 as an Apoptotic Sensitizer in Activation-Induced Cell Death of Brain Microglia
J. Immunol., December 1, 2003; 171(11): 5802 - 5811.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
H. Y. Kim, E. J. Park, E.-h. Joe, and I. Jou
Curcumin Suppresses Janus Kinase-STAT Inflammatory Signaling through Activation of Src Homology 2 Domain-Containing Tyrosine Phosphatase 2 in Brain Microglia
J. Immunol., December 1, 2003; 171(11): 6072 - 6079.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
K. Zhu, M. A. Amin, M. J. Kim, K. J. Katschke Jr., C. C. Park, and A. E. Koch
A Novel Function for a Glucose Analog of Blood Group H Antigen as a Mediator of Leukocyte-Endothelial Adhesion via Intracellular Adhesion Molecule 1
J. Biol. Chem., June 6, 2003; 278(24): 21869 - 21877.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
E. J. Park, S. Y. Park, E.-h. Joe, and I. Jou
15d-PGJ2 and Rosiglitazone Suppress Janus Kinase-STAT Inflammatory Signaling through Induction of Suppressor of Cytokine Signaling 1 (SOCS1) and SOCS3 in Glia
J. Biol. Chem., April 18, 2003; 278(17): 14747 - 14752.
[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 © 2002 by the American Society for Biochemistry and Molecular Biology.