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In this study, we investigated arginine transport activity and the expression of the related transporter genes during the differentiation of monocytes to macrophages. We show here that the induction of THP-1 monocyte differentiation by PMA markedly increases the expression of SLC7A7 mRNA and of y+LAT1 protein and consequently, the activity of system y+L-mediated arginine transport. Conversely, the activity of system y+ decreases during macrophage differentiation as a result of a reduction in CAT1 protein expression. The PMA-induced, macrophage-differentiated phenotype and the increased activity of system y+L through the induction of SLC7A7 gene are mediated by the specific activation of PKC\u03b2. SLC7A7 gene silencing causes a significant reduction of system y+L activity and a subsequent, marked increase of arginine and lysine cell content, thus suggesting that in macrophagic cells, system y+L activity is mainly directed outwardly. Differentiating agents other than PMA, i.e., VD3 and ATRA, are equally effective in the stimulation of system y+L transport activity through the increased expression of SLC7A7 mRNA and y+LAT1 protein. Moreover, we found that also during differentiation of human monocytes from peripheral blood SLC7A7 mRNA and system y+L activity are increased. These findings point to SLC7A7 gene as a marker of macrophage differentiation.<\/jats:p>","DOI":"10.1189\/jlb.0910510","type":"journal-article","created":{"date-parts":[[2011,5,18]],"date-time":"2011-05-18T04:24:46Z","timestamp":1305692686000},"page":"293-303","source":"Crossref","is-referenced-by-count":43,"title":["Arginine transport in human monocytic leukemia THP-1 cells during macrophage differentiation"],"prefix":"10.1093","volume":"90","author":[{"given":"Amelia","family":"Barilli","sequence":"first","affiliation":[{"name":"Department of Experimental Medicine, Section of General and Clinical Pathology, University of Parma , Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bianca Maria","family":"Rotoli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of General and Clinical Pathology, University of Parma , Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Visigalli","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of General and Clinical Pathology, University of Parma , Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ovidio","family":"Bussolati","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of General and Clinical Pathology, University of Parma , Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gian C","family":"Gazzola","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of General and Clinical Pathology, University of Parma , Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Dall'Asta","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Section of General and Clinical Pathology, University of Parma , Parma, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,5,17]]},"reference":[{"key":"2023033004524640800_","volume-title":"Immunobiology, the Immune System in Health and Disease","author":"Janeway","year":"2005"},{"key":"2023033004524640800_","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1007\/978-1-59745-396-7_3","article-title":"Macrophage activation: classical versus alternative","volume":"531","author":"Classen","year":"2009","journal-title":"Methods Mol. 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