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Cytokines and glucocorticoids differentially regulate APN/CD13 and DPPIV/CD26 enzyme activities in cultured human dermal fibroblasts

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Abstract

Cultured human dermal fibroblasts coexpress two cell surface ectopeptidases, aminopeptidase N (APN/CD13) and dipeptidyl peptidase IV (DPPIV/CD26). These enzymes catalyze the removal of a single amino acid or a dipeptide from the N-termini of oligopeptides, respectively. They are also localized in a differential pattern in normal, non-sun-exposed, adult skin, a finding that supports the supposition that these enzymes might have different functions in the skin, but relatively little is known about their functions in the skin. A better understanding of how the activities of these enzymes are regulated should increase our understanding of their functions in the skin. APN/CD13 was routinely expressed at higher levels on cultured fibroblasts than was DPPIV/CD26. Treatment of cultured fibroblasts with specific factors differentially modulated the activities of these enzymes. APN/CD13 was significantly upregulated by treatment with interleukin-4 (IL-4), interferon γ (IFNγ), and the glucocorticoids dexamethasone and hydrocortisone. In contrast, the regulation of DPPIV/CD26 activity was found to be different and more complex. This enzyme was consistently upregulated by IL-1α and IL-1β, but consistently downregulated by glucocorticoids, tumor necrosis factor α (TNFα) and transforming growth factor β1 (TGFβ1). Thus, although these two enzymes are expressed on the same populations of cultured cells, their activities are differentially regulated. This finding, along with their differential distribution in normal skin, suggests that APN/CD13 and DPPIV/CD26 have different functions in the skin.

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Acknowledgements

We gratefully acknowledge L'Oréal Life Sciences Research (Clichy, France) for providing the funding for these studies. Drs. Thomas McCormick (Department of Dermatology, Case Western Reserve University, Cleveland, OH, USA) and Daniel Asselineau (Advanced Research, Life Sciences Section, L'Oréal Research, Clichy, France) are also gratefully acknowledged for their suggestions and critical reading of the manuscript. In addition, we would like to thank Drs. Thomas McCormick and Irwin Schafer for providing tissue and cells used in these studies.

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  1. Department of Biology, Case Western Reserve University, Cleveland, OH 44106, USA

    J. Michael Sorrell, Laure Brinon, Marilyn A. Baber & Arnold I. Caplan

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  1. J. Michael Sorrell
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  2. Laure Brinon
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  3. Marilyn A. Baber
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  4. Arnold I. Caplan
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Correspondence to J. Michael Sorrell.

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Sorrell, J.M., Brinon, L., Baber, M.A. et al. Cytokines and glucocorticoids differentially regulate APN/CD13 and DPPIV/CD26 enzyme activities in cultured human dermal fibroblasts. Arch Dermatol Res 295, 160–168 (2003). https://doi.org/10.1007/s00403-003-0417-4

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  • DOI: https://doi.org/10.1007/s00403-003-0417-4

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