Aerosolized adrenomedullin suppresses pulmonary transforming growth factor-beta1 and interleukin-1 beta gene expression in vivo.
The effect of aerosolized adrenomedullin on interleukin-1 beta and transforming growth factor (TGF)-beta1 mRNA and protein expression was studied in surfactant depleted piglets, receiving aerosolized adrenomedullin (adrenomedullin, n=6), aerosolized adrenomedullin plus i.v. N(G)-nitro-L-arginine-methylester (adrenomedullin+L-NAME, n=5), or aerosolized saline solution (control, n=6). After 8 h of aerosol interval therapy, mRNA expression of interleukin-1 beta and TGF-beta1 in lung tissue was quantified normalized to beta-actin and hypoxanthine-guanine-phosphoribosyl-transferase by real-time polymerase chain reaction (PCR). Interleukin-1 beta and TGF-beta1 protein concentration in lung tissue was quantified by enzyme-linked immunosorbent assay (ELISA). In the adrenomedullin group, interleukin-1 beta and TGF-beta1 mRNA expression was lower than in controls. Reduction for interleukin-1 beta/beta-actin was 56% (p<0.001), for interleukin-1 beta/hypoxanthine-guanine-phosphoribosyl-transferase 60% (p<0.001), for TGF-beta1/beta-actin 65.5% (p<0.001), and for TGF-beta1/hypoxanthine-guanine-phosphoribosyl-transferase 56.2% (p<0.001). Mean interleukin-1 beta protein expression was different between the groups, p<0.05 (adrenomedullin 601+/-61, Control 836+/-88 pg/mg protein). L-NAME did not antagonize adrenomedullin effect on TGF-beta1 mRNA. In conclusion, aerosolized adrenomedullin reduced pulmonary inflammatory and pro-fibrotic response.
von der Hardt
Katharina
K
Klinik für Kinder und Jugendliche der Friedrich-Alexander-Universität Erlangen-Nürnberg, Loschgestr. 15, D-91054, Erlangen, Germany.
Kandler
Michael A
MA
Popp
Karolin
K
Schoof
Ellen
E
Chada
Martin
M
Rascher
Wolfgang
W
Dötsch
Jörg
J
D053607:Adrenomedullin; D000336:Aerosols; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D015870:Gene Expression; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D013552:Swine; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1
D000336:Aerosols; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007375:Interleukin-1; D010455:Peptides; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D053607:Adrenomedullin