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Differential inflammatory activation of IL-6 (-/-) astrocytes.
- Source :
-
Cytokine [Cytokine] 2005 Apr 21; Vol. 30 (2), pp. 47-55. - Publication Year :
- 2005
-
Abstract
- IL-6 is a major immunomodulatory cytokine with neuroprotective activity. The absence of interleukin-6 (IL-6) results in increased vulnerability of dopaminergic neurons to the neurotoxicant, MPTP, and a compromised reactive microgliosis. To determine how astrogliosis may contribute to nigrostriatal degeneration in IL-6 (-/-) mice, the inflammatory profiles of astrocytes of IL-6 genotype were compared. Fourteen cytokines and four chemokines were simultaneously assayed in the supernatants of LPS-stimulated primary astrocyte cultures. In a time course of 6, 18 and 48 h and LPS stimulations of 0, 0.1, 1, 10 and 100 ng/ml, IL-6 (-/-) astrocytes secreted significantly greater amounts of the pro-inflammatory cytokines IL-1alpha, IL-1beta and TNFalpha than did IL-6 (+/+) cells. Elevated levels of IL-10 and IL-12p40 were only detected at 48 h post-stimulation with greater IL-10 in IL-6 (-/-) supernatants and greater IL-12p40 in IL-6 (+/+) supernatants. IL-6 (+/+) astrocytes produced more G-CSF and GM-CSF when compared with IL-6 (-/-) astrocytes. Chemokine levels were greater in supernatants of IL-6 (+/+) astrocytes than IL-6 (-/-) cells prior to 48 h post-stimulation. At that time, higher levels of MIP-1alpha were maintained in IL-6 (+/+) supernatant, while similar levels of MCP-1 in supernatants of both IL-6 (+/+) and IL-6 (-/-) cells were measured. Additionally, LPS (100 ng/ml) resulted in greater levels of KC and Rantes in IL-6 (-/-) astrocyte supernatants compared with IL-6 (+/+) supernatants at that time. These results suggest that the autocrine modulatory activities of IL-6 affect multiple cytokine secretory pathways, which could participate in neurodegenerative processes.
- Subjects :
- Animals
Astrocytes drug effects
Astrocytes metabolism
Cells, Cultured
Chemokine CCL5 metabolism
Cytokines immunology
Dose-Response Relationship, Immunologic
Female
Inflammation pathology
Inflammation Mediators immunology
Inflammation Mediators metabolism
Interleukin-6 immunology
Interleukin-6 metabolism
Lipopolysaccharides toxicity
MPTP Poisoning immunology
Male
Mice
Astrocytes immunology
Chemokines metabolism
Cytokines metabolism
Inflammation metabolism
Interleukin-6 genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1043-4666
- Volume :
- 30
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Cytokine
- Publication Type :
- Academic Journal
- Accession number :
- 15804595
- Full Text :
- https://doi.org/10.1016/j.cyto.2004.11.007