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We recently demonstrated that marijuana cannabinoids are potent inducers of MDSCs. In the current study, we investigated the epigenetic mechanisms through which THC, an exogenous cannabinoid, induces MDSCs and compared such MDSCs with the nai\u00a8ve MDSCs found in BM of BL6 (WT) mice. Administration of THC into WT mice caused increased methylation at the promoter region of DNMT3a and DNMT3b in THC-induced MDSCs, which correlated with reduced expression of DNMT3a and DNMT3b. Furthermore, promoter region methylation was decreased at Arg1 and STAT3 in THC-induced MDSCs, and consequently, such MDSCs expressed higher levels of Arg1 and STAT3. In addition, THC-induced MDSCs secreted elevated levels of S100A8, a calcium-binding protein associated with accumulation of MDSCs in cancer models. Neutralization of S100A8 by use of anti-S100A8 (8H150) in vivo reduced the ability of THC to trigger MDSCs. Interestingly, the elevated S100A8 expression also promoted the suppressive function of MDSCs. Together, the current study demonstrates that THC mediates epigenetic changes to promote MDSC differentiation and function and that S100A8 plays a critical role in this process.<\/jats:p>","DOI":"10.1189\/jlb.1a1014-479r","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T08:53:38Z","timestamp":1424940818000},"page":"677-688","source":"Crossref","is-referenced-by-count":64,"title":["\u03949-Tetrahydrocannabinol-mediated epigenetic modifications elicit myeloid-derived suppressor cell activation via STAT3\/S100A8"],"prefix":"10.1093","volume":"97","author":[{"given":"Jessica Margaret","family":"Sido","sequence":"first","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine , Columbia, South Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoming","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine , Columbia, South Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prakash S","family":"Nagarkatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine , Columbia, South Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitzi","family":"Nagarkatti","sequence":"additional","affiliation":[{"name":"Department of Pathology, Microbiology, and Immunology, University of South Carolina School of Medicine , Columbia, South Carolina , USA"},{"name":"WJB Dorn Veterans Affairs Medical Center , Columbia, South Carolina , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,2,20]]},"reference":[{"key":"2023013012470976800_B1","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/2051-1426-1-10","article-title":"Myeloid derived suppressor cells\u2014a new therapeutic target in the treatment of cancer","volume":"1","author":"Wesolowski","year":"2013","journal-title":"J. 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