title: IL-25 enhances HSV-1 replication by inhibiting filaggrin expression, and acts synergistically with Th2 cytokines to enhance HSV-1 replication.
abstract: Atopic dermatitis (AD) is characterized by epidermal barrier defects and recurrent microbial skin infections. AD patients with a history of eczema herpeticum (ADEH+) have more severe skin disease and more highly T helper type 2 (Th2)-polarized immune responses as compared with uncomplicated AD (ADEH-). However, the mechanisms linking epidermal barrier defects and viral skin infection are not well understood. Recently, it has been reported that interleukin-25 may play a role in augmenting Th2 responses. We examined protein expression of IL-25 in the skin biopsies from normal subjects (n=10), ADEH- (n=18), ADEH+ (n=7), and psoriasis (n=9). IL-25 expression was increased in the skin from ADEH-, ADEH+, and psoriasis as compared with normal skin, and was significantly greater in lesional ADEH+ skin than in lesional ADEH- skin. Importantly, we demonstrated that IL-25 enhances herpes simplex virus (HSV)-1 and vaccinia virus replication by inhibiting filaggrin expression, and IL-25 acts synergistically with IL-4 and IL-13 to enhance HSV-1 replication in vitro. In contrast, IFN-γ inhibited HSV-1 replication in vitro. In addition, we demonstrate that filaggrin is a critical protein to inhibit HSV-1 replication because filaggrin small interfering RNA knockdown enhances HSV-1 replication in vitro. Filaggrin breakdown products, however, inhibited HSV-1 replication in vitro.
authors: Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.
authors: Byung Eui
authors: BE
authors: Kim
authors: Department of Pediatrics, National Jewish Health, Denver, Colorado, USA.
authors: Lianghua
authors: L
authors: Bin
authors: Department of Pediatrics, National Jewish Health, Denver, Colorado, USA; Department of Allergy and Clinical Immunology, Ajou University School of Medicine, Suwon, Korea.
authors: Young-Min
authors: YM
authors: Ye
authors: Department of Medicine, National Jewish Health, Denver, Colorado, USA.
authors: Preveen
authors: P
authors: Ramamoorthy
authors: Department of Pediatrics, National Jewish Health, Denver, Colorado, USA; Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. Electronic address: leungd@njhealth.org.
authors: Donald Y M
authors: DYM
authors: Leung
mesh_terms: D001706:Biopsy; D003876:Dermatitis, Atopic / Q000150:complications / Q000378:metabolism* / Q000821:virology; D000091344:Filaggrin Proteins; D005786:Gene Expression Regulation; D020868:Gene Silencing; D005838:Genotype; D018259:Herpesvirus 1, Human / Q000502:physiology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D020381:Interleukin-17 / Q000502:physiology*; D015847:Interleukin-4 / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000378:metabolism*; D007617:Kaposi Varicelliform Eruption / Q000150:complications / Q000378:metabolism* / Q000821:virology; D011565:Psoriasis / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D012867:Skin / Q000378:metabolism; D012871:Skin Diseases / Q000821:virology; D018418:Th2 Cells / Q000378:metabolism*; D014616:Vaccinia virus / Q000378:metabolism; D014777:Virus Diseases / Q000378:metabolism; D014779:Virus Replication
chemical_list: C000717249:FLG protein, human; D000091344:Filaggrin Proteins; C486701:IL25 protein, human; D018793:Interleukin-13; D020381:Interleukin-17; D007381:Intermediate Filament Proteins; D034741:RNA, Small Interfering; D015847:Interleukin-4; D007371:Interferon-gamma
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