Objective
Several studies support the interaction between the endocrine and the immune systems during inflammation and have demonstrated the critical role of the hypothalamic-pituitary-adrenal (HPA) axis in this process.
We have demonstrated proinflammatory effects of Corticotropin Releasing Hormone (CRH) in vivo and we have confirmed these findings by the compromised inflammatory responses of the Crh-deficient (Crh-/-) mice to a variety of stimuli.
We have also shown reduced proinflammatory cytokine expression and lower NF-B activation in Crh-/- splenocytes exposed to lipopolysaccharide (LPS), and induction of NF-B activity by CRH in mouse thymocytes.
Although the above findings indicate a pathway mediating the proinflammatory effects of CRH, the signalling pathways involved in the CRH-induced NF-B activation and up-regulation of proinflammatory cytokines remain elusive.
Our working hypotheses are that the proinflammatory effects of CRH during Gram-negative infection are mediated by the I-B/NF-B and the MAP kinases systems and that CRH plays a role in the molecular regulation of the expression of Toll-like receptor (TLR)-4, that is critical in the transduction of the lipopolysaccharide (LPS) signalling inside the cells.
Mouse and human macrophage cell lines, and primary cells from Crh-/- mice will be used to address the following:
- Does CRH play a role in the regulation of TLR4 or its effects are exerted at the level of the adapter proteins and/or transcription factors activated by this receptor? What is the biological significance of the CRH-induced TLR4 regulation on the transcriptional activation of proinflammatory mediators of Gram negative infections?
- What is the effect of Crh-deficiency on the molecular regulation of TLR4 expression? The overall significance of this proposal is related to our understanding on the participation of CRH, a representative neuropeptide with immunomodulatory properties, in the regulation of the innate responses to Gram-negative bacteria the cause of infections associated wit h high morbidity.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences neurobiology
- natural sciences biological sciences microbiology bacteriology
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- medical and health sciences clinical medicine endocrinology
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Programme(s)
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Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
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Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP6-2002-MOBILITY-12
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Funding Scheme
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Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
IRG - Marie Curie actions-International re-integration grants
Coordinator
ATHENS
Greece
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