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Here we used human intestinal epithelial cells (IEC) and three different isolates of the protozoan parasite <jats:italic>Giardia intestinalis<\/jats:italic> to investigate the role of arginine and arginine-metabolizing enzymes during intestinal protozoan infections.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>RNA expression analyses of major arginine-metabolizing enzymes revealed the arginine-utilizing pathways in human IECs (differentiated Caco-2 cells) grown <jats:italic>in vitro<\/jats:italic>. Most genes were constant or down-regulated (e.g. arginase 1 and 2) upon interaction with <jats:italic>Giardia<\/jats:italic>, whereas inducible NO synthase (iNOS) and ornithine decarboxylase (ODC) were up-regulated within 6\u00a0h of infection. <jats:italic>Giardia<\/jats:italic> was shown to suppress cytokine-induced iNOS expression, thus the parasite has both iNOS inducing and suppressive activities. Giardial arginine consumption suppresses NO production and the NO-degrading parasite protein flavohemoglobin is up-regulated in response to host NO. In addition, the secreted, arginine-consuming giardial enzyme arginine deiminase (GiADI) actively reduces T-cell proliferation <jats:italic>in vitro<\/jats:italic>. Interestingly, the effects on NO production and T cell proliferation could be reversed by addition of external arginine or citrulline.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>\n              <jats:italic>Giardia<\/jats:italic> affects the host\u2019s arginine metabolism on many different levels. Many of the effects can be reversed by addition of arginine or citrulline, which could be a beneficial supplement in oral rehydration therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1186\/1471-2180-13-256","type":"journal-article","created":{"date-parts":[[2013,11,14]],"date-time":"2013-11-14T10:02:13Z","timestamp":1384423333000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":83,"title":["The role of arginine and arginine-metabolizing enzymes during Giardia \u2013 host cell interactions in vitro"],"prefix":"10.1186","volume":"13","author":[{"given":"Britta","family":"Stadelmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt","family":"Hanevik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mattias K","family":"Andersson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oystein","family":"Bruserud","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Staffan G","family":"Sv\u00e4rd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2013,11,14]]},"reference":[{"key":"2133_CR1","first-page":"3","volume":"218","author":"SG Svard","year":"2003","unstructured":"Svard SG, Hagblom P, Palm JE: Giardia lamblia \u2013 a model organism for eukaryotic cell differentiation. 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