A distinct role for interleukin-6 as a major mediator of cellular adjustment to an altered culture condition

J Cell Biochem. 2015 Nov;116(11):2552-62. doi: 10.1002/jcb.25200.

Abstract

Tissue microenvironment adjusts biological properties of different cells by modulating signaling pathways and cell to cell interactions. This study showed that epithelial-mesenchymal transition (EMT)/ mesenchymal-epithelial transition (MET) can be modulated by altering culture conditions. HPV E6/E7-transfected immortalized oral keratinocytes (IHOK) cultured in different media displayed reversible EMT/MET accompanied by changes in cell phenotype, proliferation, gene expression at transcriptional, and translational level, and migratory and invasive activities. Cholera toxin, a major supplement to culture medium, was responsible for inducing the morphological and biological changes of IHOK. Cholera toxin per se induced EMT by triggering the secretion of interleukin 6 (IL-6) from IHOK. We found IL-6 to be a central molecule that modulates the reversibility of EMT based not only on the mRNA level but also on the level of secretion. Taken together, our results demonstrate that IL-6, a cytokine whose transcription is activated by alterations in culture conditions, is a key molecule for regulating reversible EMT/MET. This study will contribute to understand one way of cellular adjustment for surviving in unfamiliar conditions.

Keywords: CHOLERA TOXIN; CULTURE CONDITION; EPITHELIAL MESENCHYMAL TRANSITION (EMT); IL-6; MESENCHYMAL EPITHELIAL TRANSITION (MET).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Culture Techniques / methods
  • Cell Line
  • Cell Movement
  • Cell Proliferation / drug effects
  • Cellular Microenvironment
  • Cholera Toxin / pharmacology*
  • Culture Media / chemistry*
  • Epithelial-Mesenchymal Transition
  • Humans
  • Interleukin-6 / genetics*
  • Interleukin-6 / metabolism*
  • Keratinocytes / cytology*
  • Keratinocytes / transplantation
  • MCF-7 Cells
  • Neoplasm Transplantation
  • Phenotype
  • Up-Regulation
  • Zebrafish / embryology

Substances

  • Culture Media
  • IL6 protein, human
  • Interleukin-6
  • Cholera Toxin