{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T20:27:25Z","timestamp":1761596845835},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T00:00:00Z","timestamp":1081814400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Experimental Dermatology"],"published-print":{"date-parts":[[2004,4]]},"abstract":"<jats:p><jats:bold>Abstract:\u2002<\/jats:bold> Human keratinocytes are known to express the protease\u2010activated receptors, PAR\u20101 and PAR\u20102. Activation of PAR\u20101 results in increased proliferation, whereas PAR\u20102 activation results in decreased keratinocyte proliferation. Trypsin activates PAR\u20101 and in higher concentrations, PAR\u20102. The aim of this study was to evaluate the overall effect of trypsin on keratinocyte proliferation in a mouse <jats:italic>in vivo<\/jats:italic> and <jats:italic>in vitro<\/jats:italic> model. Daily topical application of 0.3\u2013300\u2003pmol trypsin\/cm<jats:sup>2<\/jats:sup> on hairless mouse skin induced dose\u2010dependent epidermal hyperproliferation as determined by an increase in 5\u2010bromo\u20102\u2032\u2010deoxyuridine incorporation of up to eight\u2010fold in basal keratinocytes and an up to three\u2010fold increase in keratinocyte layers. This was accompanied by an increased transepidermal water loss. These effects of trypsin were abolished by the addition of the trypsin inhibitor <jats:italic>n<\/jats:italic>\u2010<jats:italic>p<\/jats:italic>\u2010tosyl\u2010<jats:sc>l<\/jats:sc>\u2010lysine\u2010chloromethyl ketone. Histological analysis revealed acanthosis, hypergranulosis, and spongiosis in the epidermis as well as vasodilatation and an inflammatory infiltrate in the upper dermis. In the murine keratinocyte cell line PAM\u2010212 activation of PAR\u20101 with specific activating peptides resulted in a calcium influx and an increase of proliferation, whereas activation of PAR\u20102 caused a diminished proliferation. Incubation with trypsin, PAR\u20101\u2010, and PAR\u20102\u2010activating peptides induced cytokine\u2010induced neutrophil chemoattractant (KC) mRNA expression as a marker for inflammation in PAM\u2010212 in a dose\u2010dependent manner. In conclusion, our results suggest that trypsin induces <jats:italic>in vivo<\/jats:italic> epidermal proliferation and inflammation. Proliferation seems not to be signaled by PAR activation, but PAR\u20102\u2010induced KC chemokine expression may contribute in part to trypsin\u2010induced inflammation.<\/jats:p>","DOI":"10.1111\/j.0906-6705.2004.00159.x","type":"journal-article","created":{"date-parts":[[2004,4,13]],"date-time":"2004-04-13T15:51:34Z","timestamp":1081871494000},"page":"234-241","source":"Crossref","is-referenced-by-count":22,"title":["Trypsin induces epidermal proliferation and inflammation in murine skin"],"prefix":"10.1111","volume":"13","author":[{"given":"Ulf","family":"Meyer\u2010Hoffert","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christina","family":"Rogalski","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefanie","family":"Seifert","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gero","family":"Schmeling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jana","family":"Wingertszahn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ehrhardt","family":"Proksch","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Wiedow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2004,4,13]]},"reference":[{"key":"e_1_2_6_2_2","first-page":"451","article-title":"Die verdauung als histologsche methode","volume":"1","author":"Ewald A","year":"1877","journal-title":"Verh Naturhist Ver Heidelb"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1159\/000255534"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0536.1994.tb00696.x"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.1998.274.6.C1429"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1006\/pupt.2001.0285"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10806"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000050620.37260.75"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004030000168"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2567.1998.00528.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199808)176:2<365::AID-JCP15>3.0.CO;2-2"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01658.x"},{"key":"e_1_2_6_13_2","first-page":"743","article-title":"Differential regulation of human keratinocyte growth and differentiation by a novel family of protease\u2010activated receptors","volume":"8","author":"Derian C K","year":"1997","journal-title":"Cell Growth Differ"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0022-202x.2001.01650.x"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi0003341"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615617"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(85)90236-4"},{"key":"e_1_2_6_18_2","first-page":"4827","article-title":"Evaluation of a soluble tetrazolium\/formazan assay for cell growth and drug sensitivity in culture using human and other tumor cell lines","volume":"48","author":"Scudiero D A","year":"1988","journal-title":"Cancer Res"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1159\/000254410"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38361-9"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.20.9151"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.7.1940"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1084\/jem.168.4.1395"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.16.6367"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1111\/1523-1747.ep12616634"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1038\/328817a0"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.48.070179.001205"},{"key":"e_1_2_6_28_2","doi-asserted-by":"crossref","first-page":"7081","DOI":"10.1016\/S0021-9258(20)89612-4","article-title":"Structure\u2010function mapping of interleukin 1 precursors. 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