Regulation of expression and function of dipeptidyl peptidase 4 (DP4), DP8/9, and DP10 in allergic responses of the lung in rats.
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.
Schade
Jutta
J
Department of Functional and Applied Anatomy, Hannover Medical School, Hannover, Germany.
Stephan
Michael
M
Schmiedl
Andreas
A
Wagner
Leona
L
Niestroj
André J
AJ
Demuth
Hans-Ulrich
HU
Frerker
Nadine
N
Klemann
Christian
C
Raber
Kerstin A
KA
Pabst
Reinhard
R
von Hörsten
Stephan
S
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
C523849:DPP10 protein, rat; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C527707:Dpp8 protein, rat; C527708:Dpp9 protein, rat; D018819:Dipeptidyl Peptidase 4