DPP4 Inhibitors increase differentially the expression of surfactant proteins in Fischer 344 rats. (15th September 2014)

• Record Type: Journal Article
• Authors: Schmiedl, A.; Grützner, D.; Hoffmann, T.; von Hörsten, S.; Stephan, M.
• Is Part Of: Acta physiologica. Volume 212:Number 3(2014:Nov.)
• Page Start: 248
• Page End: 261
• Publication Date: 2014-09-15
• Subjects: Physiology -- Periodicals; Physiology -- Research -- Periodicals; 612
• DOI: 10.1111/apha.12350
• Languages: English
• ISSNs: 1748-1708

Abstract

<abstract abstract-type="main" id="apha12350-abs-0001"> <title>Abstract</title> <sec id="apha12350-sec-0001" sec-type="section"> <title>Aim</title> <p>Intact surface active agent (surfactant) composed of surfactant‐associated proteins (SPs) and lipids is necessary for respiration and prevents alveoli from collapsing. CD26, a transmembrane glycoprotein exerting dipeptidyl peptidase activity (DPP4), highly expressed in lung parenchyma, is involved in inflammatory processes. A pharmacological inhibition of DPP4 influenced not only the inflammation but also elevated the SPs. Thus, DPP4 inhibitors may be a novel drug for treatment of diseases with surfactant deficiency. Therefore, we tested firstly the hypothesis that DPP4 inhibitors increase the expression of SPs in healthy rats.</p> </sec> <sec id="apha12350-sec-0002" sec-type="section"> <title>Methods</title> <p>SP mRNA and protein expression were determined different times after nebulization of aerosolized DPP4 inhibitors [L‐isoleucine‐thiazolidide (L‐Ile‐Thia), L‐valine‐pyrrolidide (L‐Val‐Pyrr)], budesonide, saline or stereoisomers.</p> </sec> <sec id="apha12350-sec-0003" sec-type="section"> <title>Results</title> <p>Compared with negative controls (1) L‐Ile‐Thia as well as budesonide led to a significant higher and L‐Val‐Pyrr had the tendency to a significant higher expression of SP‐A mRNA 6 h after nebulization, (2) the expression of SP‐D mRNA increased significantly 6 h after nebulization with L‐Ile‐Thia and 3 and 6 h after nebulization with Val‐pyrr, (3) SP‐B mRNA levels showed significantly higher values 3 and 6 h after nebulization with L‐Val‐Pyrr, (4) protein levels of SP‐A, SP‐B and SP‐C were elevated significantly 6 h after nebulization with L‐Val‐Pyrr as well as with budesonide, and (5) phospholipids were also increased in response to DPP4 inhibition; the minimal surface tension was comparable.</p> </sec> <sec id="apha12350-sec-0004" sec-type="section"> <title>Conclusion</title> <p>DPP4 inhibition influence differently the expression of surfactant proteins in healthy rats and may be suitable to elevate surfactant synthesis in different diseases accompanied with surfactant deficiencies.</p> </sec> </abstract>