Monocytes expression of IL-12 related and IL-10 genes in association with development of colorectal cancer

• Published in: Molecular biology reports 2012-12, Vol.39 (12), p.10895-10902
• Main Authors: Stanilov, Noyko S., Miteva, Lyuba D., Dobreva, Zlatka G., Jovchev, Jovcho P., Cirovski, Geo M., Stanilova, Spaska A.
• Format: Article
• Language: English
• Subjects: Aged; Animal Anatomy; Animal Biochemistry; Biomedical and Life Sciences; c-Jun amino-terminal kinase; Case-Control Studies; Cell Transformation, Neoplastic - genetics; Colorectal cancer; Colorectal Neoplasms - genetics; Cytokines; Demography; Female; Gene expression; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Genetic Predisposition to Disease; Histology; Humans; Immune response; Interleukin 10; Interleukin 12; Interleukin-10 - genetics; Interleukin-10 - metabolism; Interleukin-12 - genetics; Interleukin-12 - metabolism; Interleukin-12 Subunit p35 - genetics; Interleukin-12 Subunit p35 - metabolism; Interleukin-12 Subunit p40 - genetics; Interleukin-12 Subunit p40 - metabolism; Interleukin-23 Subunit p19 - genetics; Interleukin-23 Subunit p19 - metabolism; Leukocytes; Life Sciences; Male; Middle Aged; Molecular biology; Monocytes; Monocytes - metabolism; Morphology; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal transduction; Transcription; Tumors
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-012-1987-z

The main regulator of anti-tumor immune response is the activity of monocytes, suggesting that the produced cytokines may have a prognostic role. This study investigates gene expression of interleukin (IL)-12-related cytokine and IL-10 in stimulated monocytes from colorectal cancer (CRC) patients. Relative quantification of IL-12A, IL-12B, IL-23A and IL-10 mRNA transcripts was performed on the third hours after stimulation by real-time qPCR. We also explored an inhibitor of JNK signaling pathway activation for the observed cytokine gene expression. A strong downregulation of IL-12B mRNA expression in CRC monocytes compared to healthy donors was observed. The rate of transcription of IL-12B in stimulated monocytes was associated with the stage of CRC. The expression of IL-12A gene in stimulated monocytes from patients with advanced was lower than early cancer. Moreover, we observed stage dependent JNK inhibition mediated reduction in IL-12A expression. The hyporesponsiveness was strongly expressed in monocytes from advanced then early stages of CRC. Expression of IL-10 mRNA was almost equally in CRC monocytes from early stages and healthy donors. We demonstrated that altered gene expression profiles of IL-12A, IL-12B, IL-23A at mRNA level in CRC monocytes was associated with tumor development and can be attributed to anticancer immune response.