Transcription profiling of brain tissue from wild type and casp1 knock-out mice treated with lipopolysaccharide or sodium chloride

ABSTRACT: The systemic inflammatory response syndrome (SIRS) is a life-threatening medical condition characterized by a severe and generalized inflammatory state that can lead to multiple organ failure and shock. The central nervous system (CNS) regulates many features of SIRS, such as fever, cardiovascular and neuroendocrine responses.

Central and systemic manifestations of SIRS can be induced by LPS or interleukin-1ß (IL-1ß) administration. The crucial role of IL-1ß in inflammation has been further highlighted by studies of mice lacking caspase 1 (casp1, also known as IL-1ß convertase), a protease that cleaves pro-IL-1ß into mature IL-1ß. Indeed, casp1 knockout (casp1-/-) mice survive lethal doses of LPS. The key role of IL-1ß in sickness behavior and its de-novo expression in the CNS during inflammation led us to test the hypothesis that IL-1ß plays a major role modulating the brain transcriptome during SIRS.

We show here a genetic background environment effect caused by LPS administration in casp1-/- when compared to wild-type mice affecting the expression several genes, such as chemokines, GTPases, the metalloprotease ADAMTS1, IL-1RA, the inducible nitric oxide synthase (NOS2) and cyclooxygenase-2 (COX-2) were differentially increased by. Our findings may contribute to the understanding of the molecular changes that take place within the CNS during sepsis and SIRS and the development of new therapies for these serious conditions. Our results indicate that those genes may also play a role in several neuropsychiatric conditions in which inflammation has been implicated, and indicate that casp1 might be a potential therapeutic target for such disorders.

ORGANISM(S): Mus musculus

SUBMITTER: Claudio Mastronardi 

PROVIDER: E-MEXP-1017 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress