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Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 02/06 Podcast
Influence of Atrial Natriuretic Peptide on inflammatory pathways in the lung

Influence of Atrial Natriuretic Peptide on inflammatory pathways in the lung

Fakultät für Chemie und Pharmazie - Digitale Hochschulschriften der LMU - Teil 02/06 vor 20 Jahren

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The cardiovascular hormone ANP is known to exert anti-inflammatory
properties in macrophages and endothelial cells. This work provides
new insight into the inflammatory signalling pathways influenced by
the ANP in the lung. For these purposes, the effects of ANP on both
alveolar epithelial cells and a model of LPS-induced lung
inflammation were characterized. In alveolar epithelial cells, ANP
was shown to inhibit the activation of two major transcription
factors, NF-kB and AP-1, in response to TNFa. Astonishingly, this
did not result in a reduced expression of the adhesion molecule
ICAM-1. ANP was also capable to diminish the activation of AP-1 and
NF-kB in lung tissue in vivo using a mouse model of LPS-induced
septic shock. The inhibition of NF-kB activation was caused by a
delayed phosphorylation and subsequent degradation of IkBa. In
addition, ANP treatment elevated total protein levels of IkBa. p38
MAPK and Akt are important mediators in LPS-induced signalling. We
demonstrated an activation of these kinases in lung tissue in
response to i.p. LPS challenge. ANP treatment was able to lessen
this activation. Furthermore, exclusive ANP treatment resulted in
an increased p38 MAPK activation, which might contribute to the
observed impact on other pathways. ICAM-1 expression was not
impaired in whole lung tissue. ANP strongly decreased TNFa serum
levels dose-dependently, but had only a slight effect on TNFa
tissue levels. Interestingly, TNFa mRNA expression was not
significantly reduced. Taken together this work demonstrates that
ANP is able to diminish several important inflammatory pathways
which are involved in the development of acute respiratory distress
syndrome in LPS-induced sepsis.