Artikel
Angiotensin II suppresses TNFa-induced IL-6 mRNA expression via the AT2-receptor in human dermal fibroblasts
Angiotensin II suppresses TNFa-induced IL-Angiotensin II über den AT2-Rezeptor verringert die durch TNFalpha induzierte Expression von Il-6 in humanen, dermalen Fibroblasten
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Veröffentlicht: | 8. August 2006 |
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Gliederung
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Recently, we demonstrated the presence of a complete renin-angiotensin-system in human skin. However, the characterisation of cutaneous actions of angiotensin II (Ang II) is only at the very beginning. Aiming to test whether Ang II may be involved in cutaneous inflammation, we examined IL-6 expression in response to Ang II with or without co-stimulation by TNFalpha and distinguished between AT1- and AT2-receptor mediated responses. Human primary dermal fibroblasts (passage 3 to 5) were isolated from female thoracic skin derived in the course of cosmetic breast surgery. Fibroblasts were stimulated with Ang II (10-7 M) for 24 hours and co-incubated with irbesartan (10-5 M; AT1-receptor antagonist) or PD 123319 (10-5 M; AT2-receptor antagonist), respectively. The same experiment was performed on a second set of cells, additionally treated with TNFalpha (10 ng/ml) in order to stimulate Il-6 expression and to examine the effect of Ang II on elevated Il-6 levels. Il-6 mRNA was detected by Real-Time-PCR.Ang II stimulated Il-6 expression fivefold. This stimulation could be inhibited by irbesartan, but not by PD 123319. TNFalpha caused a marked increase in Il-6 expression, which could be inhibited by AT2-receptor stimulation (Ang II in the presence of irbesartan). Thus, in human dermal fibroblasts, Il-6 expression is stimulated by TNFalpha and to a lesser extent by Ang II via the AT1-receptor. In contrast, Ang II via the AT2-receptor diminishes TNFalpha induced Il-6 expression. Consequently, Ang II may be involved in cutaneous inflammation by a dual mechanism: it acts pro-inflammatory via the AT1-receptor and anti-inflammatory via the AT2-receptor.