RT Journal Article
SR Electronic
T1 Induction of the TGF-beta pseudoreceptor BAMBI by nontypeable haemophilus influenzae (NTHi) and its impact on TGF-beta induced effects
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP P2496
VO 44
IS Suppl 58
A1 Dorothee Wilpsbaeumer
A1 Kristina Rohmann
A1 Jan Rupp
A1 Peter Zabel
A1 Sebastian Marwitz
A1 Torsten Goldmann
A1 Klaus Dalhoff
A1 Daniel Droemann
YR 2014
UL http://erj.ersjournals.com/content/44/Suppl_58/P2496.abstract
AB NTHi is the most frequently isolated pathogen in acute exacerbations of COPD. NTHI induces the TGF-beta Pseudoreceptor BAMBI, which has been shown to act as an antagonist on TGF-beta signaling.To investigate the effects of BAMBI expression, experiments were performed in A549 cells and lung tissue of a mouse model (BAMBI+/+mouse vs. BAMBI-/-mouse). A549 cells were transfected with BAMBI-si-RNA and murine lung tissue was cultivated ex vivo. The cytokine release has been investigated by ELISA and Multiplexanalysis of cell- and tissue-supernatants.After in vitro and ex vivo-infection, marked proinflammatory effects of A549 cells and murine lung tissue, measured as the secretion of CXCL-8, were observed (A549: Med 24h 507+96 pg/ml vs. NTHi 106 cfu/ml 24h 1391+250 pg/ml, p<0,01, n=7; lung BAMBI +/+mouse Med 24h 15902+7277 pg/ml vs. NTHI 106 cfu/ml 24h 98622+ 11709 pg/ml, p<0,01, n=6; lung BAMBI -/-mouse: Med 24h 26662+5640 pg/ml vs. NTHI 106 cfu/ml 24h 102954+8642 pg/ml, p<0,01, n=10).Furthermore we demonstrated that there was a significant decrease of TGF-beta secretion after stimulation (Med 24h 1188+148 pg/ml vs. NTHi 106cfu/ml 24h 1004+98 pg/ml, p<0,05), whereas the TGF-beta secretion increased after transfection with BAMBI-si-RNA (Med 24h 1112+107 pg/ml vs. NTHi 106cfu/ml 24h 1252+134 pg/ml, p=0,05, n=5).Our results show the inhibitory effect of BAMBI on TGF-beta signalling after infection with NTHi. Additionally there are indications of antinflammatory effects of BAMBI in the knockout model.This mechanism moght have relevant influence on lung tissue remodeling and repair functions after chronic infections in COPD patients.