2. Academic Validation
  3. Interleukin (IL)-22 from IL-20 Subfamily of Cytokines Induces Colonic Epithelial Cell Proliferation Predominantly through ERK1/2 Pathway

Interleukin (IL)-22 from IL-20 Subfamily of Cytokines Induces Colonic Epithelial Cell Proliferation Predominantly through ERK1/2 Pathway

  • Int J Mol Sci. 2019 Jul 15;20(14):3468. doi: 10.3390/ijms20143468.
Md Moniruzzaman 1 2,  Ran Wang 2,  Varinder Jeet 3 4,  Michael A McGuckin 5,  Sumaira Z Hasnain 6 7 8
Affiliations

Affiliations

  • 1 Faculty of Medicine, The University of Queensland, Brisbane, QLD 4067, Australia.
  • 2 Immunopathology Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia.
  • 3 Australian Prostate Cancer Research Centre-Queensland, Institute of Health Biomedical Innovation (IHBI), Queensland University of Technology, Brisbane, QLD 4102, Australia.
  • 4 Macquarie University Centre for the Health Economy, Macquarie University, NSW 2109, Australia.
  • 5 Faculty of Medicine, Dentistry and Health Sciences, the University of Melbourne, VIC 3052, Australia.
  • 6 Faculty of Medicine, The University of Queensland, Brisbane, QLD 4067, Australia. sumaira.hasnain@mater.uq.edu.au.
  • 7 Immunopathology Group, Mater Research Institute-The University of Queensland, Translational Research Institute, Brisbane, QLD 4102, Australia. sumaira.hasnain@mater.uq.edu.au.
  • 8 Australian Infectious Disease Research Centre, University of Queensland, Brisbane, QLD 4067, Australia. sumaira.hasnain@mater.uq.edu.au.
PMID: 31311100 DOI: 10.3390/ijms20143468
Abstract

The interleukin (IL)-20 subfamily of cytokines consists of IL-19, IL-20, IL-22, IL-24, and IL-26, and the expression of IL-20, IL-22, and IL-24 is reported to be higher in the colon of patients with ulcerative colitis. Although the receptors for these cytokines are highly expressed in the colon epithelium, their effects on epithelial renewal are not clearly understood. This study evaluated the effects of IL-20, IL-22, and IL-24 in epithelial renewal using the LS174T human colon Cancer epithelial cell line. LS174T cells were treated with IL-20, IL-22, and IL-24 (25, 50, and 100 ng/mL) and a live-cell imaging system was used to evaluate the effects on cell proliferation. Following treatment, the signaling pathways contributing to cell proliferation were investigated through Western blotting in LS174T cells and downstream transcriptional changes through qRT-PCR in LS174T cells, and RNA-Seq in primary murine intestinal epithelial cells. Our results demonstrated that only IL-22 promoted LS174T cell proliferation, mediated via extracellular-signal-regulated kinase (ERK)1/2-mediated downstream regulation of p90RSK, c-Jun, and transcriptional changes of TRIM15 and STOM. IL-22 also promoted expression of ERK1/2-independent genes such as DDR2, LCN2, and LRG1, which are known to be involved in cell proliferation and migration. This study suggests that IL-22 induces cell proliferation in highly proliferative cells such as intestinal epithelial cells.

Keywords

ERK1/2; IL-20; IL-22; IL-24; cell proliferation; wound healing.

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