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

Mol Biol Rep. 2012 Dec;39(12):10895-902. doi: 10.1007/s11033-012-1987-z. Epub 2012 Oct 10.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Case-Control Studies
  • Cell Transformation, Neoplastic / genetics*
  • Colorectal Neoplasms / genetics*
  • Demography
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • 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
  • Male
  • Middle Aged
  • Monocytes / metabolism*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • IL10 protein, human
  • IL12A protein, human
  • IL12B protein, human
  • IL23A protein, human
  • Interleukin-12 Subunit p35
  • Interleukin-12 Subunit p40
  • Interleukin-23 Subunit p19
  • RNA, Messenger
  • Interleukin-10
  • Interleukin-12