Analysis of IFN-kappa expression in pathologic skin conditions: downregulation in psoriasis and atopic dermatitis.

Abstract

Interferon-kappa (IFN-kappa) is a type I IFN expressed by keratinocytes, monocytes and dendritic cells (DCs). In human keratinocytes, it is produced in response to double-stranded RNA (dsRNA) and other IFNs and protects from viral infections. In monocytes and DCs, IFN-kappa induces tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) and inhibits lipopolysaccharide (LPS)-induced IL-12. In this study, we evaluated IFN-kappa expression in skin lesions of patients with common immune-mediated inflammatory disorders using immunohistochemical techniques. IFN-kappa was not detectable in healthy skin but was strongly expressed in allergic contact dermatitis and lichen planus-affected skin. IFN-kappa was localized mainly in basal and suprabasal keratinocytes and in some leukocytes infiltrating the dermis. In contrast, IFN-kappa expression in psoriatic or atopic dermatitis (AD) pidermis was weak and detectable in only 2 of 5 patients examined. Consistently, cultured keratinocytes and monocytes obtained from psoriatic and AD patients expressed null or low levels of IFN-kappa in response to IFN-gamma, which strongly upregulates IFN-kappa in normal keratinocytes. IFN-kappa accumulated in keratinocyte cytoplasm and plasma membrane, and only limited amounts were released extracellularly. Soluble IFN-kappa did not influence keratinocyte proliferation or chemokine and membrane molecule expression, and only its membrane-associated form activated IFN-stimulated response element (ISRE) signaling. Given the difference in IFN-kappa expression levels in the skin disorders examined, IFN-kappa presence or deficiency might have different pathogenetic consequences depending also on other disease-specific intrinsic alterations.

• Authors: Claudia Scarponi, Bernardetta Nardelli, David W Lafleur, Paul A Moore, Stefania Madonna, Ornella De Pità, Giampiero Girolomoni, Cristina Albanesi
• Journal: Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research (J Interferon Cytokine Res) Vol. 26 Issue 3 Pg. 133-40 (Mar 2006) ISSN: 1079-9907 [Print] United States
• PMID: 16542135 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interferon Type I
• interferon kappa
• Interferon-gamma

Topics

• Adult
• Animals
• Biopsy
• Blotting, Western
• CHO Cells
• Cell Membrane (metabolism)
• Cells, Cultured
• Cricetinae
• Cytoplasm (metabolism)
• Dermatitis, Atopic (metabolism, pathology)
• Down-Regulation (immunology)
• Enzyme-Linked Immunosorbent Assay
• Female
• Flow Cytometry
• Gene Expression Regulation (immunology)
• Humans
• Immunohistochemistry
• Interferon Type I (analysis, metabolism)
• Interferon-gamma (pharmacology)
• Keratinocytes (drug effects, metabolism, pathology)
• Leukocytes, Mononuclear (drug effects, metabolism)
• Male
• Middle Aged
• Psoriasis (metabolism, pathology)