The expression of TLR pathway molecules in peripheral blood mononuclear cells and their relationship with tumor invasion and cytokine secretion in laryngeal carcinoma

Adv Med Sci. 2012 Jun 1;57(1):124-35. doi: 10.2478/v10039-011-0058-3.

Abstract

Purpose: The aim of this study was to analyze of TLRs mRNA expression in peripheral blood mononuclear cells as potential biomarkers of neoplastic lesions progress and to evaluate their role in the possible mechanisms responsible for the secretion of cytokines in laryngeal cancer.

Material/methods: The analysis of TLR2, TLR4, TRAF6, IRAK1 expression in isolated PBMCs by the reverse transcription PCR (RT-PCR) analysis as well as IL-6, IL-8 and TNF-α levels in supernatants of peripheral blood mononuclear cells from 55 patients with carcinoma of the larynx was performed by ELISA. The invasiveness of carcinoma was evaluated according to tumor front grading, TFG.

Results: We noted that tumors with a well-defined borderline were characterized by significantly higher values of the average expression of TRAF6. Our research also confirmed that more aggressive carcinomas according to TFG, with a more dispersed type of invasion were characterized by significantly lower values of the average expression of IRAK1. Moreover, we observed that tumors with the invasion of cartilage were characterized by significantly lower values of the average expression of TLR4. In addition, the relationships of TLR2 with IL-6 and TNF-α level were highlighted. Significant interconnections were also found between the TLR4 and IL-8, TNF-α, IL-6 secretion after stimulation. The relationships of TRAF6 with IL-8 production after stimulation were noted.

Conclusions: Our findings confirmed the implication of the TLRs pathway molecules in proinflammatory cytokine secretions and their importance as encouraging potential indicators for assessment of the degree of aggressive tumor phenotype.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-6 / metabolism
  • Interleukin-8 / metabolism
  • Laryngeal Neoplasms / metabolism*
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • Middle Aged
  • Reverse Transcriptase Polymerase Chain Reaction
  • TNF Receptor-Associated Factor 6 / genetics
  • TNF Receptor-Associated Factor 6 / metabolism
  • Toll-Like Receptor 2 / genetics
  • Toll-Like Receptor 2 / metabolism
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / metabolism
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / metabolism*
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Interleukin-6
  • Interleukin-8
  • TLR2 protein, human
  • TNF Receptor-Associated Factor 6
  • Toll-Like Receptor 2
  • Toll-Like Receptor 4
  • Toll-Like Receptors
  • Tumor Necrosis Factor-alpha