Induction of CXCL10 chemokine in adrenocortical cells by stimulation through toll-like receptor 3

Mol Cell Endocrinol. 2013 Jan 5;365(1):75-83. doi: 10.1016/j.mce.2012.09.004. Epub 2012 Sep 16.

Abstract

Addison's disease is a prototypic organ-specific autoimmune disease affecting the adrenal cortex. The CXC chemokine ligand 10 (CXCL10) is expressed early in viral infections, and is produced by primary adrenocortical cells stimulated by certain cytokines. CXCL10 is also elevated in the serum of Addison's disease patients. We therefore investigated if the viral RNA substitute polyinosine-polycytidylic acid (poly (I:C)) could influence the cytokine induced production of CXCL10 by adrenocortical cells. We found that poly (I:C) could induce CXCL10 in NCI-H295R adrenocortical carcinoma cells, either alone or synergistically along with cytokines interferon-γ and tumor necrosis factor-α. This effect was found to be mediated by toll-like receptor 3 and both nuclear factor κB (NFκB) and signal transducer and activator of transcription-1 (STAT1), but not type I interferons, seemed to be involved. We propose that the combination of environmental and endogenous factors presented here, could contribute to the multifactorial pathogenesis of autoimmune Addison's disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Addison Disease / blood
  • Addison Disease / immunology
  • Addison Disease / metabolism
  • Adrenal Cortex / cytology
  • Adrenal Cortex / drug effects
  • Adrenal Cortex / immunology*
  • Adrenal Cortex / metabolism
  • Animals
  • Autoantigens / adverse effects*
  • Autoantigens / genetics
  • Autoantigens / metabolism
  • Cattle
  • Cell Line
  • Cells, Cultured
  • Chemokine CXCL10 / agonists
  • Chemokine CXCL10 / blood
  • Chemokine CXCL10 / metabolism*
  • Humans
  • Interferon Inducers / pharmacology
  • Interferon-gamma / metabolism
  • Leukocytes, Mononuclear / drug effects
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Poly I-C / pharmacology
  • Receptors, CXCR3 / metabolism
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / metabolism
  • STAT1 Transcription Factor / antagonists & inhibitors
  • STAT1 Transcription Factor / metabolism
  • Steroid 21-Hydroxylase / adverse effects
  • Steroid 21-Hydroxylase / genetics
  • Steroid 21-Hydroxylase / metabolism
  • Toll-Like Receptor 3 / agonists*
  • Toll-Like Receptor 3 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Autoantigens
  • CXCL10 protein, human
  • CXCR3 protein, human
  • Chemokine CXCL10
  • Interferon Inducers
  • NF-kappa B
  • Receptors, CXCR3
  • Recombinant Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • TLR3 protein, human
  • Toll-Like Receptor 3
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma
  • Steroid 21-Hydroxylase
  • Poly I-C