Decrease of ceramides with long-chain fatty acids in psoriasis: Possible inhibitory effect of interferon gamma on...

Area of Science:

• Dermatology
• Biochemistry
• Molecular Biology

Background:

• Decreased fatty acid (FA) chain length of ceramide (CER) is linked to increased interferon-gamma (IFN-γ) expression in psoriasis.
• The precise molecular mechanisms underlying this association and its impact on psoriasis pathogenesis are not fully understood.

Purpose of the Study:

• To elucidate the relationship between FA chain length of CER, IFN-γ, and key transcriptional factors implicated in psoriasis.
• To investigate the role of IFN-γ in regulating CER metabolism and its associated enzymes and transcription factors.

Main Methods:

• CER profiling based on FA chain length and class in murine epidermis and human stratum corneum (SC) from psoriasis patients and controls.
• Quantitative RT-PCR to measure the expression of lipid synthetic enzymes, including elongases (ELOVLs), in murine epidermis.
• In vitro studies using keratinocytes to assess the association of IFN-γ with enzymes and transcription factors involved in long-chain CER generation.

Main Results:

• A significant reduction in long-chain CERs was observed in both psoriasis-like murine epidermis and human psoriatic SC.
• Expression levels of ELOVL1, ELOVL4, and ceramide synthase 3 (CerS3) were significantly decreased in psoriasis-like murine epidermis and IFN-γ-treated keratinocytes.
• Expression of transcriptional factors, including peroxisome proliferator-activated receptor (PPAR), was significantly reduced in IFN-γ-treated keratinocytes.

Conclusions:

• IFN-γ may regulate ELOVL and CerS expression by down-regulating transcriptional factors like PPAR.
• PPARs or liver X receptor agonists could potentially serve as therapeutic agents to restore CER FA lengthening in psoriasis.