Glucocorticoids Exacerbate Lipopolysaccharide-Induced Signaling in the Frontal Cortex and Hippocampus in a Dose-Dependent Manner

Although the anti-inflammatory actions of glucocorticoids (GCs) are well established, evidence has accumulated showing that proinflammatory GC effects can occur in the brain, in a poorly understood manner. Using electrophoretic mobility shift assay, real-time PCR, and immunoblotting, we investigated the ability of varying concentrations of corticosterone (CORT, the GC of rats) to modulate lipopolysaccharide (LPS)-induced activation of NF-kappa B (nuclear factor kappa B), expression of anti- and proinflammatory factors and of the MAP (mitogen-activated protein) kinase family [ERK (extracellular signal-regulated kinase), p38, and JNK/ SAPK (c-Jun N-terminal protein kinase/ stress-activated protein kinase)], and AKT. In the frontal cortex, elevated CORT levels were proinflammatory, exacerbating LPS effects on NF-kappa B, MAP kinases, and proinflammatory gene expression. Milder proinflammatory GCs effects occurred in the hippocampus. In the absence of LPS, elevated CORT levels increased basal activation of ERK1/ 2, p38, SAPK/ JNK, and AKT in both regions. These findings suggest that GCs do not uniformly suppress neuroinflammation and can even enhance it at multiple levels in the pathway linking LPS exposure to inflammation.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

C.S. from Fundacao de Amparo a Pesquia do Estado de Sao Paulo (FAPESP)[2002/02298-2]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

C.S. from Fundacao de Amparo a Pesquia do Estado de Sao Paulo (FAPESP)[2004/11041-0]

C.S. from Fundacao de Amparo a Pesquia do Estado de Sao Paulo (FAPESP)[04/11042-7]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)[201059/2003-7]

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Adler Foundation

Adler Foundation

MICINN

MICINN

National Institutes of Health (NIH)[R01 MH53814]

U.S. National Institutes of Health (NIH)

U.S. National Institutes of Health (NIH)

National Institutes of Health (NIH)[P01 NS37520]