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However, the pathogenic status of<jats:named-content content-type=\"genus-species\">Blastocystis<\/jats:named-content>infection remains unclear. In this study, we found that<jats:named-content content-type=\"genus-species\">Blastocystis<\/jats:named-content>antigens induced abundant expression of proinflammatory cytokines, including interleukin 1\u03b2 (IL-1\u03b2), IL-6, and tumor necrosis factor alpha (TNF-\u03b1), in mouse intestinal explants, in mouse colitis colon, and in macrophages. Further investigation utilizing RAW264.7 murine macrophages showed that<jats:named-content content-type=\"genus-species\">Blastocystis<\/jats:named-content>treatment in RAW264.7 macrophages induced the activation of ERK, JNK, and p38, the three major groups of mammalian mitogen-activated protein (MAP) kinases that play essential roles in the expression of proinflammatory cytokines. ERK inhibition in macrophages significantly suppressed both mRNA and protein expression of IL-6 and TNF-\u03b1 and mRNA expression of IL-1\u03b2. On the other hand, JNK inhibition resulted in reductions in both c-Jun and ERK activation and significant suppression of all three proinflammatory cytokines at both the mRNA and protein levels. Inhibition of p38 suppressed only IL-6 protein expression with no effect on the expression of IL-1\u03b2 and TNF-\u03b1. Furthermore, we found that serine proteases produced by<jats:named-content content-type=\"genus-species\">Blastocystis<\/jats:named-content>play an important role in the induction of ERK activation and proinflammatory cytokine expression by macrophages. Our study thus demonstrated for the first time that<jats:named-content content-type=\"genus-species\">Blastocystis<\/jats:named-content>could induce the expression of various proinflammatory cytokines via the activation of MAP kinases and that infection with<jats:named-content content-type=\"genus-species\">Blastocystis<\/jats:named-content>may contribute to the pathogenesis of inflammatory intestinal diseases through the activation of inflammatory pathways in host immune cells, such as macrophages.<\/jats:p>","DOI":"10.1128\/iai.02279-14","type":"journal-article","created":{"date-parts":[[2014,8,26]],"date-time":"2014-08-26T03:35:50Z","timestamp":1409024150000},"page":"4789-4801","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["Differential Regulation of Proinflammatory Cytokine Expression by Mitogen-Activated Protein Kinases in Macrophages in Response to Intestinal Parasite Infection"],"prefix":"10.1128","volume":"82","author":[{"given":"Mei Xing","family":"Lim","sequence":"first","affiliation":[{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chin Wen","family":"Png","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Crispina Yan Bing","family":"Tay","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua Ding Wei","family":"Teo","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huipeng","family":"Jiao","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Lehming","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin Shyong Wei","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongliang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Immunology Programme, Life Sciences Institute, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.immunol.20.100301.064816"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-030409-101225"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11908-009-0073-8"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00022-08"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(97)00046-7"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.protis.2013.05.003"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-009-1485-y"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"41","DOI":"10.7883\/yoken.JJID.2004.41","article-title":"Intestinal parasitic infections in HIV\/AIDS and HIV seronegative individuals in a teaching hospital, Ethiopia","volume":"57","author":"Hailemariam G","year":"2004","unstructured":"HailemariamGKassuAAbebeGAbateEDamteDMekonnenEOtaF. 2004. 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