Presentation Abstract

Title: IL-25 Down-regulates Epidermal Barrier Proteins and Enhances Viral Replication
Presentation Time: Monday, Mar 05, 2012, 2:30 PM - 2:45 PM
Author Block: B. Kim, L. Bin, D. Y. Leung;
National Jewish Health, Denver, CO.
Abstract: Rationale: Interleukin (IL)-25 is a recently reported Th2 promoting cytokine that is over-expressed in atopic dermatitis (AD) skin. In the current study, we investigated whether IL-25 impairs epidermal differentiation and host defense against viral infection.
Methods: Normal human keratinocytes (NHK) were differentiated for 6 days in the presence or absence of IL-25, Th1 or Th2 cytokines. In some experiments, the cells were incubated with HSV-1 for an additional 24 hours. The expression of filaggrin (FLG)-1, loricrin (LOR) and involucrin (IVL), herpes simplex virus 1 (HSV-1), human beta defensin-3 (HBD-3) and cathelicidin (LL-37) was evaluated using real time RT-PCR or by Western blotting. The siRNA technique was used to silence FLG-1 gene expression.
Results: IL-25 down-regulated the expression of FLG-1 and LOR. IVL, HBD-3 and LL-37 were not modulated by IL-25. HSV-1 replication was significantly increased in NHK pretreated with IL-25 (mean: 1.12±0.06) as compared to cells without IL-25 pretreatment (mean: 0.83±0.01) (P<0.05). HSV-1 replication was further increased in NHK pretreated with a combination of IL-25 and Th2 cytokines compared to IL-25 (P<0.01) or Th2 cytokines alone (P<0.05). In contrast, interferon gamma reduced HSV-1 replication (P<0.001). Silencing gene expression of FLG-1 significantly enhanced HSV-1 replication (P<0.01).
Conclusions: IL-25 down-regulates epidermal barrier proteins and enhances HSV-1 replication. In addition, Th2 cytokines act synergistically with IL-25 to enhance HSV-1 replication.

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