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Effects of estrogen against LPS-induced inflammation and toxicity in primary rat glial and neuronal cultures

Department of Clinical Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Abed N. Azab

Department of Clinical Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, Israel, Recanati School for Community Health Professions, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel

Jacob Kaplanski

Department of Clinical Pharmacology, Ben-Gurion University of the Negev, Beer-Sheva, Israel, jacobk{at}bgu.ac.il

Several lines of evidence link inflammation with neurodegenerative diseases, which are aggravated by the age-related decline in estrogen levels in postmenopausal women. Lipopolysaccharide (LPS) is used widely to stimulate glial cells to produce pro-inflammatory mediators such as NO, PGE₂, and TNF-, and was found to be toxic in high doses. We examined the effects of a physiological dose of 17ß-estradiol (E2) against LPS-induced inflammation and toxicity (cell death) in rat primary glial and neuronal cultures. Cultures were treated with 0.1 nM E2 for 24 h and then exposed to LPS 0.5—200 µg/ml for another 24 h. Levels of NO, PGE₂, and TNF- in the culture medium were determined by the Griess reaction assay, radio-immunoassay, and enzyme-linked immunoassay, respectively. Cell death was quantified by measuring the leakage of lactate dehydrogenase (LDH) into the medium from dead or dying cells using the non-radioactive cytotoxicity assay. E2 significantly reduced the LPS-induced increase in NO and TNF- (but not PGE₂) production in glial cells. PGE ₂ and TNF- were undetectable in neuronal cultures, while only basal levels of NO were detected, even after stimulation with LPS. Moreover, pretreatment with E2 significantly reduced LPS-induced cell death, as measured by the release of LDH, in both glial and neuronal cultures. These results suggest that the neuroprotective effects attributed to E2 are derived, at least in part, from its anti-inflammatory and cytoprotective effects in both glial and neuronal cells.

Key Words: Estrogen • inflammation • neurodegeneration • cytotoxicity

Journal of Endotoxin Research, Vol. 13, No. 3, 158-166 (2007)
DOI: 10.1177/0968051907080428


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