Abstract
Type I interferon kappa (IFNκ) is selectively expressed in human keratinocytes. Herpes simplex virus-1 (HSV-1) is a human pathogen that infects keratinocytes and causes lytic skin lesions. Whether IFNκ plays a role in keratinocyte host defense against HSV-1 has not been investigated. In this study, we found that IFNκ mRNA expression was induced by addition of recombinant IFNκ and poly (I:C); and its expression level was significantly greater than IFNa2, IFNb1, and IFNL1 in both undifferentiated and differentiated normal human epidermal keratinocytes (NHEKs) under resting and stimulation conditions. Although IFNe was expressed at a relatively higher level than other IFNs in resting undifferentiated NHEK, its expression level did not change after stimulation with recombinant IFNκ and poly (I:C). HSV-1 infection inhibited gene expression of IFNκ and IFNe in NHEK. Silencing IFNκ in NHEK led to significantly enhanced HSV-1 replication in both undifferentiated and differentiated NHEK compared to scrambled siRNA-transfected cells, while the addition of recombinant IFNκ significantly reduced HSV-1 replication in NHEK. In addition, we found that IFNκ did not regulate protein expression of NHEK differentiation markers. Our results demonstrate that IFNκ is the dominant type of IFNs in keratinocytes and it has an important function for keratinocytes to combat HSV-1 infection.
Highlights
The interferon (IFN) κ gene was identified in 2001 [1]
To evaluate the relative importance of IFNκ in keratinocytes compared to other IFN family members, we investigated IFNκ expression levels in normal human epidermal keratinocytes (NHEKs) cells under both undifferentiated and differentiated conditions in the presence and absence of recombinant human IFNκ (rhIFNκ), poly (I:C), and Herpes simplex virus-1 (HSV-1)
IFNe mRNA was expressed at greater levels compared to other IFNs in undifferentiated NHEK, it was not upregulated further by rhIFNκ
Summary
The interferon (IFN) κ gene was identified in 2001 [1]. IFNκ was initially found to be constitutively expressed in human proliferating primary keratinocytes and could be induced significantly by IFNβ, IFN-γ, and encephalomyocarditis virus (ECMV) [1]. IFNκ is expressed by limited cell sources, it activates the same signaling pathway as other type I IFNs by receptors of IFNRA1/IFNRA2 [1]. Because it is constitutively expressed in keratinocytes, IFNκ has been investigated for its role in human papillomavirus- (HPV-) involved human diseases. High-risk HPV were reported to inhibit IFNκ gene transcription in human cervical keratinocytes, and its expression is reduced and undetectable in HPV-positive human cervical keratinocytes [3,4,5]
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