PMID- 19822498 OWN - NLM STAT- MEDLINE DCOM- 20100301 LR - 20111117 IS - 1499-3872 (Print) VI - 8 IP - 5 DP - 2009 Oct TI - Effect of insulin on functional status of cord blood-derived dendritic cells and on dendritic cell-induced CTL cytotoxicity against pancreatic cancer cell lines. PG - 529-34 AB - BACKGROUND: Dendritic cells (DCs) are the most important antigen-presenting cells in the human body, and DCs with different mature status possess different or even opposite functions. This study was designed to explore the influence of insulin on the functional status of cord blood-derived DCs and on DC-induced cytotoxic T lymphocyte (CTL) activity against pancreatic cancer cell lines. METHODS: Mononuclear cells were isolated from fresh cord blood. Interleukin-4 (IL-4) and granulocyte-macrophage colony-stimulating factor (GM-CSF) were used to induce or stimulate the mononuclear cells. Insulin at different concentrations served to modify DCs, and then DC morphology, number, and growth status were assessed. The DC immunophenotype was detected with a flow cytometer. The IL-12 in DC supernatant was determined by ELISA. DC functional status was evaluated by the autologous mixed lymphocyte reaction. T lymphocytes were induced by insulin-modified DCs to become CTLs. The CTL cytotoxicity against pancreatic cancer cell lines was determined. RESULTS: Mononuclear cells from cord blood can be differentiated into DCs by cytokine induction and insulin modification. With the increase in insulin concentration (2.5-25 mg/L), the expression of DC HLA-DR, CD1alpha, CD80, and CD83 was significantly increased, the DC ability to secrete IL-12 was significantly improved, DC function to activate autologous lymphocytes was significantly enhanced, and the cytotoxicity of CTLs induced by insulin-modified DCs against pancreatic cancer cell lines was significantly strengthened. CONCLUSIONS: Insulin may facilitate DC induction and maturation, and improve the reproductive activity of autologous lymphocytes. The cytotoxicity of CTLs induced by insulin-modified DCs against pancreatic cancer cell lines was significantly enhanced. Insulin may serve as a factor modifying DCs and inducing CTLs in vitro in insulin biotherapy. FAU - Liu, Qiu-Liang AU - Liu QL AD - Department of Surgery, First Affiliated Hospital, Zhengzhou University, Zhengzhou 450052, China. FAU - Wang, Yi-Sheng AU - Wang YS FAU - Wang, Jia-Xiang AU - Wang JX LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Singapore TA - Hepatobiliary Pancreat Dis Int JT - Hepatobiliary & pancreatic diseases international : HBPD INT JID - 101151457 RN - 0 (Insulin) RN - 0 (Interleukin-2) SB - IM MH - Adenocarcinoma/*pathology MH - Apoptosis/drug effects MH - Cell Communication/physiology MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - Dendritic Cells/cytology/*drug effects/*physiology MH - Dose-Response Relationship, Drug MH - Fetal Blood/cytology MH - Humans MH - Immunophenotyping MH - Insulin/*pharmacology MH - Interleukin-2/metabolism MH - Pancreatic Neoplasms/*pathology MH - T-Lymphocytes, Cytotoxic/cytology/*drug effects/*physiology EDAT- 2009/10/14 06:00 MHDA- 2010/03/02 06:00 CRDT- 2009/10/14 06:00 PHST- 2009/10/14 06:00 [entrez] PHST- 2009/10/14 06:00 [pubmed] PHST- 2010/03/02 06:00 [medline] AID - 1282 [pii] PST - ppublish SO - Hepatobiliary Pancreat Dis Int. 2009 Oct;8(5):529-34.