The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice.
Herpes simplex virus type 1 (HSV-1) induces an ocular chronic immunoinflammatory syndrome named herpetic stromal keratitis that can lead to vision impairment and blindness. We have reported that the synthetic brassinosteroid (22S,23S)-3beta-bromo-5alpha,22,23-trihydroxystigmastan-6-one, designated as 2, is a potent antiviral in vitro and reduces the incidence of murine herpetic stromal keratitis, although it does not exert an antiviral effect in vivo. In the present report, we investigated whether brassinosteroid 2 may play a role in the modulation of the response of epithelial and immune cells to HSV-1 infection. Compound 2 blocked HSV-1-induced activation of NF-kappaB by inhibiting its translocation to the nucleus of infected corneal and conjunctival cells in vitro, as well as significantly reduced the secretion of TNF-alpha in infected NHC cells. Conversely, IL-6 production was enhanced by compound 2 after HSV-1 infection in both cell types. The production of these cytokines was considerably reduced in a LPS-stimulated macrophage cell line after treatment with compound 2. In conclusion, brassinosteroid 2 would be playing a modulating effect as an inductor or inhibitor, depending on the cell type involved. The improvement of disease observed in mice could be a balance between both, the immunostimulating and immunosuppressive effects of brassinosteroid 2 in vivo.
Laboratory of Virology, Department of Biochemistry, School of Science, University of Buenos Aires, Pabellón II, Piso 4to., Ciudad Universitaria, 1428 Buenos Aires, Argentina.
Flavia M
FM
Michelini
Alejandro
A
Berra
Laura E
LE
Alché
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002778:Cholestanones / Q000494:pharmacology* / Q000627:therapeutic use*; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D019573:Epithelium, Corneal / Q000187:drug effects / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000187:drug effects; D018259:Herpesvirus 1, Human / Q000235:genetics; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D016849:Keratitis, Herpetic / Q000188:drug therapy*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D013256:Steroids / Q000494:pharmacology* / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000235:genetics
C493970:3-bromo-5,22,23-trihydroxystigmastan-6-one; D000998:Antiviral Agents; D002778:Cholestanones; D007155:Immunologic Factors; D015850:Interleukin-6; D016328:NF-kappa B; D013256:Steroids; D014409:Tumor Necrosis Factor-alpha; D014759:Viral Envelope Proteins