| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
,
,
* Department of Infectious Diseases, Faculty of Medicine and the Wellcome Trust Centre for Clinical Tropical Medicine, Imperial College (Hammersmith Campus), London, United Kingdom;
Departments of Microbiology and Pathology, Universidad Peruana Cayetano Heredia, Lima, Peru;
Cysticercosis Unit, Instituto Nacional de Ciencias Neurológicas, Lima, Peru;
Department of International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205; and
¶ School of Veterinary Medicine, Universidad Nacional Mayor de San Marcos, Lima, Peru
Neurocysticercosis, caused by infection with larval Taenia solium, is a major cause of epilepsy worldwide. Larval degeneration, which is symptomatic, results in inflammatory cell influx. Astrocytes, the most abundant cell type and major cytokine-producing cell within the CNS, may be important in orchestrating inflammatory responses after larval degeneration. We investigated the effects of direct stimulation and of conditioned medium from T. solium larval Ag (TsAg)-stimulated monocytes (CoMTsAg) on neutrophil and astrocyte chemokine release. CoMTsAg, but not control conditioned medium, stimulated astrocyte CCL2/MCP-1 (161.5 ± 16 ng/ml), CXCL8/IL-8 (416 ± 6.2 ng/ml), and CXCL10/IFN-
-inducible protein (9.07 ± 0.6 ng/ml) secretion after 24 h, whereas direct astrocyte or neutrophil stimulation with TsAg had no effect. There was rapid accumulation of CCL2 and CXCL8 mRNA within 1 h, with somewhat delayed expression of CXCL10 mRNA initially detected 8 h poststimulation. Neutralizing anti-TNF-
inhibited CoMTsAg-induced CCL2 mRNA accumulation by up to 99%, causing total abolition of CXCL10 and up to 77% reduction in CXCL8 mRNA. CoMTsAg induced maximal nuclear binding of NF-
B p65 and p50 by 1 h, with IB and IB
decay within 15 min. In addition, CoMTsAg induced transient nuclear binding of AP-1, which peaked 4 h poststimulation. In NF-B blocking experiments using pyrrolidine dithiocarbamate, CoMTsAg-induced CCL2 secretion was reduced by up to 80% (p = 0.0006), whereas CXCL8 was inhibited by up to 75% (p = 0.0003). In summary, the data show that astrocytes are an important source of chemokines following larval Ag stimulation. Such chemokine secretion is NF-B dependent, likely to involve AP-1, and is regulated in a paracrine loop by monocyte-derived TNF-.
This article has been cited by other articles:
|
|
 |
|
  W. Stenzel, S. Soltek, M. Sanchez-Ruiz, S. Akira, H. Miletic, D. Schluter, and M. Deckert Both TLR2 and TLR4 Are Required for the Effective Immune Response in Staphylococcus aureus-Induced Experimental Murine Brain Abscess Am. J. Pathol., January 1, 2008; 172(1): 132 - 145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. E. Harris, J. A. Green, P. T. Elkington, and J. S. Friedland Monocytes infected with Mycobacterium tuberculosis regulate MAP kinase-dependent astrocyte MMP-9 secretion J. Leukoc. Biol., February 1, 2007; 81(2): 548 - 556. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
