Abstract:
:Interleukin-1 beta (IL-1 beta) is a pro-inflammatory cytokine produced in the brain by endogenous microglial cells responding to injury. Levels of IL-1 beta are elevated in several neurodegenerative disorders, including Alzheimer's disease. IL-1 beta, which can act as a mitogen for astrocytes, also elicits the expression and secretion of multiple factors and paracrine 'second messengers' such as other cytokines, nerve growth factor, prostaglandins and nitric oxide that may in turn modulate neuronal and glial responses to injury. Utilizing giant, high-resolution two-dimensional gel electrophoresis, we have sought to more fully define the potential range of protein mediators that are secreted by astrocytes treated with IL-1 beta. In cultured rat astrocytes, we observe dramatic increases in the secretion of eight different protein species after 24 h of treatment with human recombinant IL-1 beta (1 U/ml). Seven of the proteins are also induced by tumor necrosis factor-alpha or basic fibroblast growth factor. Based on immunoprecipitation with specific antisera, we have identified three of these proteins as plasminogen activator inhibitor type-1, ceruloplasmin, and complement component C3. The identities of the other proteins, including the IL-1 beta-specific induction, are currently unknown. Characterization of these downstream modulators of IL-1 beta action complements gene-based approaches and will provide a better understanding of astrocyte responses to injury as well as markers for astrocyte activation in neurodegenerative diseases.
journal_name
Neurochem Intjournal_title
Neurochemistry internationalauthors
Chang JW,Young DA,Coleman PD,O'Banion MKdoi
10.1016/s0197-0186(01)00042-0subject
Has Abstractpub_date
2001-11-01 00:00:00pages
349-59issue
5-6eissn
0197-0186issn
1872-9754pii
S0197018601000420journal_volume
39pub_type
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