DPP4 Inhibitors increase differentially the expression of surfactant proteins in Fischer 344 rats

作者：Schmiedl A^*; Gruetzner D; Hoffmann T; von Hoersten S; Stephan M

来源：Acta Physiologica, 2014, 212(3): 248-261.

DOI：10.1111/apha.12350

• CD26
• DPP4
• DPP4 inhibitors
• surface tension
• surfactant proteins

AimIntact 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. %26lt;br%26gt;MethodsSP 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. %26lt;br%26gt;ResultsCompared 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 6h after nebulization, (2) the expression of SP-D mRNA increased significantly 6h after nebulization with L-Ile-Thia and 3 and 6h after nebulization with Val-pyrr, (3) SP-B mRNA levels showed significantly higher values 3 and 6h after nebulization with L-Val-Pyrr, (4) protein levels of SP-A, SP-B and SP-C were elevated significantly 6h 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. %26lt;br%26gt;ConclusionDPP4 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.

• 出版日期2014-11