Background. Glucan is an immunomodulating agent used for cancer therapy. We investigated the effects of glucan on immune cell response to prostate carcinoma. Methods. Dendritic cells (DC) were co-cultured with prostate carcinoma cells LNCaP and/or glucan, and maturation markers expression, cytokine release, and superoxide anion production were evaluated. Conditioned media from glucan-treated or untreated DC and/or LNCaP cultures were used to stimulate T lymphocytes and natural killer (NK) cells. Results. LNCaP promoted partial DC maturation and scarce IL-12 secretion. Glucan induced DC maturation but no IL-12 production by DC. However, glucan increased IL-12 release by DC co-cultured with LNCaP. Moreover, LNCaP enhanced IL-1b, IL-23, IL-6, and TNF-a secretion, but decreased superoxide anion production in glucan-stimulated DC. The NADPH oxidase inhibitor diphenyliodonium chloride (DPI) and the superoxide anion scavenger superoxide dismutase (SOD) reproduced this effect, but did not affect IL-12 secretion. Conditioned media of glucan-treated DC/LNCaP co-cultures activated IFN-g production by NK cells and Th1/Th17 generation by CD4þ lymphocytes, whereas media from DC/LNCaP co-cultured without glucan produced scarce NK and CD4þ cells responses. Experiments performed with an IL-12-blocking antibody demonstrated that these effects arise from glucan-dependent regulation of IL-12 production by DC. Conclusions. Glucan and LNCaP cooperate in induction of cytokine synthesis by DC. LNCaP enhance IL-1b, IL-23, IL-6, and TNF-a secretion by decreasing glucan-dependent NADPH oxidase activity, whereas glucan increases IL-12 production through NADPH oxidase-unrelated mechanisms. This cooperation is essential to elicit a substantial NK cells and CD4þ lymphocytes activity, pointing out a potential relevance of glucan in prostate cancer therapy.
Prostate Carcinoma Cells LNCaP and Glucan Cooperate inInduction of Cytokine Synthesis by Dendritic Cells: Effect onNatural Killer Cells and CD4+ Lymphocytes Activation
DONINI, Marta;Marongiu, Laura;FONTANA, Emanuela;DUSI, Stefano
2012-01-01
Abstract
Background. Glucan is an immunomodulating agent used for cancer therapy. We investigated the effects of glucan on immune cell response to prostate carcinoma. Methods. Dendritic cells (DC) were co-cultured with prostate carcinoma cells LNCaP and/or glucan, and maturation markers expression, cytokine release, and superoxide anion production were evaluated. Conditioned media from glucan-treated or untreated DC and/or LNCaP cultures were used to stimulate T lymphocytes and natural killer (NK) cells. Results. LNCaP promoted partial DC maturation and scarce IL-12 secretion. Glucan induced DC maturation but no IL-12 production by DC. However, glucan increased IL-12 release by DC co-cultured with LNCaP. Moreover, LNCaP enhanced IL-1b, IL-23, IL-6, and TNF-a secretion, but decreased superoxide anion production in glucan-stimulated DC. The NADPH oxidase inhibitor diphenyliodonium chloride (DPI) and the superoxide anion scavenger superoxide dismutase (SOD) reproduced this effect, but did not affect IL-12 secretion. Conditioned media of glucan-treated DC/LNCaP co-cultures activated IFN-g production by NK cells and Th1/Th17 generation by CD4þ lymphocytes, whereas media from DC/LNCaP co-cultured without glucan produced scarce NK and CD4þ cells responses. Experiments performed with an IL-12-blocking antibody demonstrated that these effects arise from glucan-dependent regulation of IL-12 production by DC. Conclusions. Glucan and LNCaP cooperate in induction of cytokine synthesis by DC. LNCaP enhance IL-1b, IL-23, IL-6, and TNF-a secretion by decreasing glucan-dependent NADPH oxidase activity, whereas glucan increases IL-12 production through NADPH oxidase-unrelated mechanisms. This cooperation is essential to elicit a substantial NK cells and CD4þ lymphocytes activity, pointing out a potential relevance of glucan in prostate cancer therapy.
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