Journalartikel

Jahr der Veröffentlichung: 2010

Seiten: 949-955

Zeitschrift: Thorax

Bandnummer: 65

Heftnummer: 11

ISSN: 0040-6376

eISSN: 1468-3296

Open Access Status: Green

DOI Link: https://doi.org/10.1136/thx.2009.134353

Verlag: BMJ Publishing Group

Abstract: 

Background Idiopathic pulmonary fibrosis (IPF) has a poor prognosis and limited responsiveness to available treatments. It is characterised by epithelial cell injury, fibroblast activation and proliferation and extracellular matrix deposition. Serotonin (5-hydroxytryptamine; 5-HT) induces fibroblast proliferation via the 5-HTR2A and 5-HTR2B receptors, but its pathophysiological role in IPF remains unclear. A study was undertaken to determine the expression of 5-HT receptors in IPF and experimental lung fibrosis and to investigate the effects of therapeutic inhibition of 5-HTR2A/B signalling on lung fibrosis in vivo and in vitro.

Methods and results Quantitative RT-PCR showed that the expression of 5-HTR1A/B and 5-HTR2B was significantly increased in the lungs of patients with IPF (n = 12) and in those with non-specific interstitial pneumonia (NSIP, n = 6) compared with transplant donors (n = 12). The expression of 5-HTR2A was increased specifically in IPF lungs but not in NSIP lungs. While 5-HTR2A protein largely localised to fibroblasts, 5-HTR2B localised to the epithelium. To assess the effects of 5HTR(2A/B) inhibition on fibrogenesis in vivo, mice were subjected to bleomycin-induced lung fibrosis and treated with the 5-HTR2A/B antagonist terguride (or vehicle) in a therapeutic approach (days 14-28 after bleomycin). Terguride-treated mice had significantly improved lung function and histology and decreased collagen content compared with vehicle-treated mice. Functional in vitro studies showed that terguride is a potent inhibitor of transforming growth factor beta(1)- or WNT3a-induced collagen production.

Conclusion The studies revealed an increased expression of 5-HTR2A specifically in IPF. Blockade of 5-HTR2A/B signalling by terguride reversed lung fibrosis and is thus a promising therapeutic approach for IPF.

Harvard-Zitierstil: Koenigshoff, M., Dumitrascu, R., Udalov, S., Amarie, O., Reiter, R., Grimminger, F., et al. (2010) Increased expression of 5-hydroxytryptamine_2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention, Thorax, 65(11), pp. 949-955. https://doi.org/10.1136/thx.2009.134353

APA-Zitierstil: Koenigshoff, M., Dumitrascu, R., Udalov, S., Amarie, O., Reiter, R., Grimminger, F., Seeger, W., Schermuly, R., & Eickelberg, O. (2010). Increased expression of 5-hydroxytryptamine_2A/B receptors in idiopathic pulmonary fibrosis: a rationale for therapeutic intervention. Thorax. 65(11), 949-955. https://doi.org/10.1136/thx.2009.134353