PMID- 24772192 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20211021 IS - 1793-9844 (Print) IS - 1793-9852 (Electronic) IS - 1793-9844 (Linking) VI - 1 IP - 3-4 DP - 2010 Sep 1 TI - ANALYSIS OF DENDRITIC CELL STIMULATION UTILIZING A MULTI-FACETED NANOPOLYMER DELIVERY SYSTEM AND THE IMMUNE MODULATOR 1-METHYL TRYPTOPHAN. PG - 239-250 AB - Dendritic cells (DCs) play a pivotal role in immune modulation. Therefore, understanding and regulating the mechanism of DC activation is paramount for functional optimization of any immunotherapy strategy. In particular, the paradoxical ability of DCs to secrete the immune suppressive enzyme indoleamine 2, 3-dioxygenase (IDO) and the suppressive cytokine IL-10 during the course of, and in response to, stimulation is of great interest. 1-Methyl-Tryptophan (1 MT) is a known inhibitor of IDO and has thus been administered in numerous in vitro and in vivo systems to block IDO activity. However, the effect 1 MT has on DCs beyond inhibiting IDO, especially in therapeutic models, has rarely been analyzed. In the current study, we have administered 1 MT via a nanopolymer-based delivery system in conjunction with an antigen (ovalbumin, OVA) and an adjuvant (CpG motif DNA) to determine both the effects of 1 MT on DCs and the resulting efficacy of the polymer-based treatments. 1 MT delivery alone, either via the polymer-based delivery vehicle or dissolved in solution, induced no significant change in DC activation as measured by surface expression of CD80, CD86, and MHCII and several secreted products such as IL-12. These same factors were upregulated however, when 1 MT was delivered in conjunction with OVA and CpG. Although soluble delivery of these components increased the levels of expression and secretion of key proteins, a differential effect of DC stimulation was seen as a result of the polymer delivery system. The T cell suppressive IL-10 secretion was lower with the polymer-based treatments and IL-12 immune-enhancing secretion was increased when 1 MT was supplemented into the polymer system. As a result, including 1 MT in the polymers along with OVA and CpG was seen to have additional effects on DC stimulation and was able to shift DCs to a state more indicative of inducing a Th1-type response. FAU - Nikitczuk, Kevin P AU - Nikitczuk KP AD - Department of Biomedical Engineering, Rutgers University, 599 Taylor Road Piscataway, New Jersey, USA. FAU - Lattime, Edmund C AU - Lattime EC AD - The Cancer Institute of New Jersey, Departments of Surgery and Molecular Genetics Microbiology, and Immunology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA. FAU - Schloss, Rene S AU - Schloss RS AD - Department of Biomedical Engineering, Rutgers University, 599 Taylor Road Piscataway, New Jersey, USA. FAU - Yarmush, Martin L AU - Yarmush ML AD - Department of Biomedical Engineering, Rutgers University, 599 Taylor Road Piscataway, New Jersey, USA. LA - eng GR - P30 CA072720/CA/NCI NIH HHS/United States GR - R01 CA042908/CA/NCI NIH HHS/United States PT - Journal Article PL - United States TA - Nano Life JT - Nano LIFE JID - 101571142 PMC - PMC3998209 MID - NIHMS553493 OTO - NOTNLM OT - 1-methyl-tryptophan OT - 1MT OT - DC OT - Dendritic cells OT - PLGA EDAT- 2010/09/01 00:00 MHDA- 2010/09/01 00:01 PMCR- 2014/04/24 CRDT- 2014/04/29 06:00 PHST- 2014/04/29 06:00 [entrez] PHST- 2010/09/01 00:00 [pubmed] PHST- 2010/09/01 00:01 [medline] PHST- 2014/04/24 00:00 [pmc-release] AID - 10.1142/S1793984410000171 [doi] PST - ppublish SO - Nano Life. 2010 Sep 1;1(3-4):239-250. doi: 10.1142/S1793984410000171.