title: PRSS14/Epithin is induced in macrophages by the IFN-γ/JAK/STAT pathway and mediates transendothelial migration.
abstract: PRSS14/Epithin (also known as matriptase and ST14), a member of the type II transmembrane serine proteases, is primarily found in a subpopulation of normal epithelial cells and in epithelial cancers. Its known functions include maintaining the epithelial barrier, thymic development, and cancer progression. In this study, we show that several macrophage cell lines and activated bone marrow-derived macrophages also express PRSS14/Epithin. Surface expression, as well as cytoplasmic expression, was detectable upon activation by IFN-γ, but not TNF-α or TGF-β. Induction of the protein appeared to be restricted to macrophages. IFN-γ showed a biphasic regulation in RAW264.7 cells, and upregulated expression was sustained for several days. This induction by IFN-γ was partially through the increase of PRSS14/Epithin mRNA production, which is downstream of the JAK pathway, shown by the inhibition by tyrphostin AG490. Using chromatin immunoprecipitation, we verified that two sites among six putative STAT1 binding sites in the PRSS14/Epithin promoter were occupied by STAT1 upon activation. Treatment with IFN-γ enhanced the serum-triggered transendothelial migration of RAW264.7 cells, but not that of PRSS14/Epithin knock-down RAW264.7 cells, although they express multiple markers such as ICAM1, CD80, and CD40 at normal levels. These data strongly suggest that PRSS14/Epithin plays an important role in the transendothelial migration of activated macrophages in the inflammatory microenvironment, and the mode of action is similar to the events in cancer metastasis.
authors.affiliation: Department of Biological Sciences, Inha University, Yonghyun-dong, Incheon 402-751, Republic of Korea.
authors.forename: Deokjae
authors.initials: D
authors.lastname: Lee
authors.forename: Hyo Seon
authors.initials: HS
authors.lastname: Lee
authors.forename: Soo Jung
authors.initials: SJ
authors.lastname: Yang
authors.forename: Hanna
authors.initials: H
authors.lastname: Jeong
authors.forename: Dong-Young
authors.initials: DY
authors.lastname: Kim
authors.forename: Sang Don
authors.initials: SD
authors.lastname: Lee
authors.forename: Jae Woo
authors.initials: JW
authors.lastname: Oh
authors.forename: Dongeun
authors.initials: D
authors.lastname: Park
authors.forename: Moon Gyo
authors.initials: MG
authors.lastname: Kim
mesh_terms: D000818:Animals; D002460:Cell Line; D002465:Cell Movement; D042783:Endothelial Cells / Q000276:immunology; D005109:Extracellular Matrix / Q000276:immunology; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D053612:Janus Kinases / Q000378:metabolism*; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000378:metabolism; D050794:STAT1 Transcription Factor / Q000378:metabolism*; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*
chemical_list: D008565:Membrane Proteins; D012333:RNA, Messenger; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; D007371:Interferon-gamma; D053612:Janus Kinases; D012697:Serine Endopeptidases; C118992:St14 protein, mouse