Colon carcinoma cell lines stimulate monocytes and lamina propria mononuclear cells to produce IL-10.
Cytokines released from tumour cells may have function as signals to neighbouring immune and inflammatory cells. Several studies have shown that the immunoregulatory cytokines IL-10 and transforming growth factor-beta1 (TGF-beta1) as well as prostaglandin-E2 (PGE2) play an important role in tumour-induced immunosuppression. The aim of the study was to investigate the effect of colon carcinoma cell lines on IL-10 production in peripheral monocytes (PBMC) and lamina propria mononuclear cells (LPMC). We examined four colon carcinoma cell lines (HT-29, Caco-2, Colo-320 and HCT-116) and determined their production of TGF-beta1, IL-10 and PGE2. Peripheral monocytes were isolated by density gradient centrifugation and LPMC were isolated from surgical specimens using a collagenase digestion method. Monocytes and LPMC were cultured with colon carcinoma cell conditioned medium or in co-culture with colon carcinoma cells. Supernatants were then determined for the production of IL-10 by ELISA assays. All colon carcinoma cell lines stimulated peripheral monocytes as well as LPMC to produce markedly increased levels of IL-10. Colon cancer cells secreted negligible levels of IL-10, but high amounts of TGF-beta1 and PGE2. Neutralization of TGF-beta1 by administration of anti-TGF-beta as well as neutralization of PGE2 with anti-PGE2 antisera reduced the IL-10 production of monocytes markedly, indicating that tumour cell-derived TGF-beta1 and PGE2 are major factors for IL-10 stimulation. In vitro stimulation of monocytes with TGF-beta1 and PGE2 could confirm that TGF-beta1 as well as PGE2 at picogram concentrations were able to prime monocytes for enhanced IL-10 production. Our results demonstrate that colon carcinoma cell lines enhance the ability of monocytes and intestinal macrophages to produce IL-10. The stimulation of monocyte IL-10 by colon cancer cell-derived TGF-beta1 and PGE2 may act as a tumour-protecting mechanism by impairing the activation of anti-tumour cytokines.
Kucharzik
T
T
Department of Medicine B, University of Münster, Germany.
Lügering
N
N
Winde
G
G
Domschke
W
W
Stoll
R
R
D002277:Carcinoma / Q000276:immunology* / Q000473:pathology; D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D017077:Culture Media, Conditioned; D015232:Dinoprostone / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis* / Q000276:immunology; D009000:Monocytes / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000276:immunology; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D015232:Dinoprostone