PT  - JOURNAL ARTICLE
AU  - David Jungck
AU  - Maria Feldmann
AU  - Chiara Wahl
AU  - Stefanie Koehler-Bachmann
AU  - Carmen Schindewolf
AU  - Erich Stoelben
AU  - Juergen Behr
AU  - Juergen Knobloch
AU  - Andrea Koch
TI  - The inflammatory response of pulmonary vascular smooth muscle cells to bacterial endotoxin is sensitive to endothelin receptor antagonism
DP  - 2012 Sep 01
TA  - European Respiratory Journal
PG  - P1954
VI  - 40
IP  - Suppl 56
4099  - http://erj.ersjournals.com/content/40/Suppl_56/P1954.short
4100  - http://erj.ersjournals.com/content/40/Suppl_56/P1954.full
SO  - Eur Respir J2012 Sep 01; 40
AB  - Bacterial infections cause exacerbations of chronic inflammatory lung diseases by aggravating airway inflammation. Current therapeutic strategies like steroid administration have proven unsatisfactory e.g. for COPD and highlight the need for new approaches.We aimed at elucidating the inflammatory response of pulmonary vascular smooth muscle cells (PVSMCs) to LPS, and whether this response is sensitive to antagonists of endothelin A receptor (ETAR) (Ambrisentan), ETBR (BQ788) or both receptors (Bosentan).PVSMCs of n=4 donors were incubated with highly purified smooth LPS (S-LPS), highly purified short-chain LPS (Re-LPS, shortest form) or M-LPS (mixture of long and short forms) of Salmonella spp. or with Lipooligosaccharide (LOS) of nonetypeable H. influenzae (NTHi) or with NTHi extract in absence or presence of endothelin receptor antagonists (10-7-10-5 M) for 72 hours and cytokines were measured by ELISA.All LPS-forms and NTHi extract induced concentration-dependent IL-6, IL-8 and GM-CSF release from PVSMCs (each p<0.05). M-LPS and LOS were most effective. The effects of M-LPS were completely abolished by polymyxin B and CLI-095 (TLR4 inhibitor) but not affected by TLR2/TLR9 inhibitors. M-LPS-induced IL-6 was reduced by all endothelin receptor antagonists (each p<0.05). IL-8 and GM-CSF were reduced by Bosentan and BQ788 but not by Ambrisentan (each p<0.05).PVSMCs contribute to the inflammatory response to bacterial infections and thus can prove to be a therapeutic target in exacerbations of chronic airway diseases. Cytokine release shows specific reactions to dual vs. selective endothelin receptor blockers which can be useful in therapy.