Inflammation, kinins, and kinin receptors
Author
Summary, in English
Bradykinin (BK) belongs to the group of vasoactive peptides, so-called kinins, which are potent inflammatory mediators. BK, once released from the human contact system, elicits a transient inflammatory response via activation of the constitutively expressed B2 receptor, which desensitizes and is internalized upon ligand binding. The kininase I metabolite of BK, desArg9BK, on the other hand mediates chronic deleterious inflammatory responses by interacting with the B1 receptor. Although normally absent, B1 receptor expression can be induced under inflammatory conditions.
The aim of the present thesis was to explore and analyze modifications in the regulation of kinins and their receptors in different settings of inflammation. It is known that BK is generated in the airways of asthmatic subjects and that disease symptoms are exacerbated during respiratory viral infections. In paper I, we report that BK induces an up-regulation of B2 receptors in human airway epithelial cells, which is in sharp contrast to other investigated cells. Further more, rhinovirus induces up-regulation of functional B1 receptors in the same cell type (paper II). Both mechanisms may render the respiratory tract more responsive to generated kinins and can significantly influence the inflammatory response and thereby symptom severity. In paper III and IV we demonstrate that the important human pathogens S. aureus and S. pyogenes can induce profound inflammatory reactions in the human host by secreting toxins that via stimulation of monocytic cells induce up-regulation of B1 receptors. Concurrently, both bacterial species are able to induce release of BK and its subsequent conversion to desArg9BK, which can evoke an over-amplification and prolongation of the inflammatory response.
Taken together, the present thesis demonstrates that kinin receptor regulation and kinin generation is affected during different settings of inflammation and we conclude that this may have a great impact on disease progression.
Department/s
Publishing year
2008
Language
English
Publication/Series
Lund University Faculty of Medicine Doctoral Dissertation Series
Volume
2008:39
Full text
- Available as PDF - 13 MB
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Document type
Dissertation
Publisher
Institutionen för kliniska vetenskaper, Lunds universitet
Topic
- Infectious Medicine
Status
Published
Supervisor
ISBN/ISSN/Other
- ISSN: 1652-8220
- ISBN: 978-91-85897-92-6
Defence date
25 April 2008
Defence time
09:15
Defence place
Segerfalksalen
Opponent
- Alexander Faussner (Dr.)