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Cyclosporine A induces nerve growth factor expression via activation of MAPK p38 and NFAT5

Joon H Lee1, Jee Won Kim, Young Sun Im

  • 1Myunggok Eye Research Institute, Kim's Eye Hospital, College of Medicine, KonYang University, ChungNam, South Korea.

Cornea
|September 14, 2011
PubMed
Abstract

Insights

Cyclosporine A (CsA) effectively induces nerve growth factor (NGF) in human corneal epithelial cells. This process involves the activation of p38 and NFAT5, highlighting a novel mechanism for NGF regulation.

Area of Science:

  • Ophthalmology
  • Cell Biology
  • Immunology

Background:

  • Nerve growth factor (NGF) plays a crucial role in ocular surface health and nerve regeneration.
  • Understanding the regulatory mechanisms of NGF expression is vital for developing therapeutic strategies for corneal diseases.

Purpose of the Study:

  • To investigate the effects of Cyclosporine A (CsA) on nerve growth factor (NGF) expression in a human corneal epithelial cell line (HCECL).
  • To elucidate the specific signaling pathways involved in CsA-mediated NGF induction.

Main Methods:

  • Human corneal epithelial cells (HCECL) were treated with varying concentrations of CsA.
  • NGF transcription and production levels were measured.
  • Luciferase assays were used to assess the activity of MAPK, NF-κB, AP-1, and NFATs.
  • NFAT5 translocation was analyzed via confocal microscopy and Western immunoblotting.
  • Inhibitors of p38 (SB20429) and NFAT5 (siRNA) were used to determine their role in NGF induction.

Main Results:

  • CsA significantly induced NGF expression in HCECL, unlike dexamethasone.
  • NGF induction was dependent on p38 phosphorylation and NFAT5 activation.
  • CsA upregulated nuclear translocation of NFAT5 but not NF-κB, AP-1, or NFAT1.
  • Inhibition of NFAT5 or p38 markedly reduced CsA-induced NGF production.

Conclusions:

  • Cyclosporine A is a potent inducer of NGF in human corneal epithelial cells.
  • CsA mediates NGF expression primarily through the activation of the p38 and NFAT5 signaling pathways.

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