title: Regulation of expression and function of dipeptidyl peptidase 4 (DP4), DP8/9, and DP10 in allergic responses of the lung in rats.
abstract: The expression of dipeptidyl peptidase 4 (DP4, CD26) affects T-cell recruitment to lungs in an experimental rat asthma model. Furthermore, the gene of the structural homologous DP10 represents a susceptibility locus for asthma in humans, and the functional homologous DP8/9 are expressed in human leukocytes. Thus, although several mechanisms may account for a role of DP4-like peptidases in asthma, detailed information on their anatomical sites of expression and function in lungs is lacking. Therefore, bronchi and lung parenchyma were evaluated using immunohistochemistry and histochemical/enzymatic activity assays, as well as quantitative real-time PCR for this family of peptidases in naïve and asthmatic rat lungs derived from wild-type F344 and DP4-deficient F344 rat strains. Surprisingly, results show not only that the induction of experimental asthma increases DP4 enzymatic activity in the bronchoalveolar lavage fluid and parenchyma, but also that DP8/9 enzymatic activity is regulated and, as well as the expression of DP10, primarily found in the bronchial epithelium of the airways. This is the first report showing a differential and site-specific DP4-like expression and function in the lungs, suggesting a pathophysiologically significant role in asthma.
authors.affiliation: Department of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
authors.forename: Jutta
authors.initials: J
authors.lastname: Schade
authors.forename: Michael
authors.initials: M
authors.lastname: Stephan
authors.forename: Andreas
authors.initials: A
authors.lastname: Schmiedl
authors.forename: Leona
authors.initials: L
authors.lastname: Wagner
authors.forename: André J
authors.initials: AJ
authors.lastname: Niestroj
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Demuth
authors.forename: Nadine
authors.initials: N
authors.lastname: Frerker
authors.forename: Christian
authors.initials: C
authors.lastname: Klemann
authors.forename: Kerstin A
authors.initials: KA
authors.lastname: Raber
authors.forename: Reinhard
authors.initials: R
authors.lastname: Pabst
authors.forename: Stephan
authors.initials: S
authors.lastname: von Hörsten
mesh_terms: D000818:Animals; D001249:Asthma / Q000201:enzymology*; D001980:Bronchi / Q000201:enzymology; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis / Q000235:genetics; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000096:biosynthesis* / Q000235:genetics; D015971:Gene Expression Regulation, Enzymologic; D007150:Immunohistochemistry; D008168:Lung / Q000201:enzymology*; D008297:Male; D016133:Polymerase Chain Reaction; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: C523849:DPP10 protein, rat; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C527707:Dpp8 protein, rat; C527708:Dpp9 protein, rat; D018819:Dipeptidyl Peptidase 4