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Identifier

000039532

Title

Μελέτη της επίδρασης των νευροπεπτιτιδίων της οικογένειας CRH στην έκφραση του υποδοχέα TLR-4

Alternative Title

Study of the role of corticotropin releasing hormone (CHR) and its related pertides on the expression of toll like receptor (TLR-4)

Author

Αλισσάφη, Θέμις

Thesis advisor

Τσατσάνης, Χρήστος

Abstract

We have previously shown that CRH augments lipopolysaccharide (LPS) -induced pro-inflammatory cytokine secretion. LPS signals via Toll like receptor-4 to mediate its pro-inflammatory actions. Expression of TLR4 is found increased during inflammation. Aim of the present study was to determine the role of CRH and its related peptides Urocortin 1 (UCN1) and Urocortin 2 (UCN2) on TLR4 expression in macrophages. Treatment of Raw264.7 macrophages with CRH, UCN1 or UCN2 upregulated TLR4 mRNA levels. The effect of CRH and Urocortins occured at the transcriptional level by activating the minimal TLR4 promoter. TLR4 promoter contains several PU.1 binding sites that drive its expression. Treatment of RAW264.7 macrophages with any of the three peptides resulted in increased PU.1 DNA binding. Induction of PU.1 binding occured via CRH2 since it was inhibited by anti-sauvagine-30. Treatment of cells with CRH, UCN or UCNII in the presence of LPS blocked the inhibitory effect of LPS to TLR4 expression indicating a possible mechanism through which CRH augments LPS-induced pro-inflammatory cytokine secretion. Our data suggest that CRH2 signals affect macrophage activation by LPS partly by upregulating TLR4 expression via activation of the transcription factor PU.1.

Language

Greek

Issue date

2004-07-01

Collection

School/Department--School of Sciences and Engineering--Department of Chemistry--Post-graduate theses

Type of Work--Post-graduate theses

Views

171

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