Involvement of nuclear factor of activated T cells in granulocyte-macrophage colony-stimulating factor production in canine keratinocytes stimulated with a cysteine protease

Abstract

Background: A previous study demonstrated that the cysteine protease of Dermatophagoides farinae induced production of granulocyte-macrophage colony-stimulating factor (GM-CSF) in a canine epidermal keratinocyte progenitor cell line (CPEK); however, the molecular mechanism has not been elucidated.

Hypothesis/objectives: Given that the transcription of GM-CSF mRNA in human lymphocytes is mainly regulated by the nuclear factor of activated T cells (NFAT), it is hypothesized that NFAT also contributes to GM-CSF production in canine keratinocytes stimulated with a cysteine protease.

Methods: Nuclear translocation of NFAT was evaluated in CPEK cells in the absence or presence of the cysteine protease papain. We also investigated whether blockade of NFAT could inhibit GM-CSF production.

Results: Papain-induced nuclear translocation of NFAT, producing GM-CSF, was partly inhibited by ciclosporin.

Conclusions and clinical importance: The results suggest that GM-CSF production mediated by the cysteine protease is regulated not only by NFAT but also by unknown signalling pathways in canine keratinocytes.