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)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one, designated as 2, is...
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todo:paper_09600760_v108_n1-2_p164_Michelini2023-10-03T15:53:21Z The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice Michelini, F.M. Berra, A. Alché, L.E. Brassinosteroid HSV-1 IL-6 Immunomodulatory activity Murine herpetic stromal keratitis NF-κB TNF-α 3beta bromo 5alpha,22,23 trihydroxystigmastan 6 one brassinosteroid immunoglobulin enhancer binding protein interleukin 6 lipopolysaccharide tumor necrosis factor alpha unclassified drug animal cell antiviral activity article controlled study cornea cell cytokine production cytokine release herpes simplex keratitis Herpes simplex virus 1 human human cell immunomodulation immunostimulation immunosuppressive treatment macrophage mouse nonhuman Animals Antiviral Agents Cell Nucleus Cells, Cultured Cholestanones Epithelial Cells Epithelium, Corneal Gene Expression Regulation, Viral Herpesvirus 1, Human Humans Immunologic Factors Interleukin-6 Keratitis, Herpetic Macrophages Mice NF-kappa B Steroids Tumor Necrosis Factor-alpha Viral Envelope Proteins Human herpesvirus 1 Murinae Mus 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)-3β-bromo-5α,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-κB by inhibiting its translocation to the nucleus of infected corneal and conjunctival cells in vitro, as well as significantly reduced the secretion of TNF-α 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. © 2007 Elsevier Ltd. All rights reserved. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_09600760_v108_n1-2_p164_Michelini |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
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R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Brassinosteroid HSV-1 IL-6 Immunomodulatory activity Murine herpetic stromal keratitis NF-κB TNF-α 3beta bromo 5alpha,22,23 trihydroxystigmastan 6 one brassinosteroid immunoglobulin enhancer binding protein interleukin 6 lipopolysaccharide tumor necrosis factor alpha unclassified drug animal cell antiviral activity article controlled study cornea cell cytokine production cytokine release herpes simplex keratitis Herpes simplex virus 1 human human cell immunomodulation immunostimulation immunosuppressive treatment macrophage mouse nonhuman Animals Antiviral Agents Cell Nucleus Cells, Cultured Cholestanones Epithelial Cells Epithelium, Corneal Gene Expression Regulation, Viral Herpesvirus 1, Human Humans Immunologic Factors Interleukin-6 Keratitis, Herpetic Macrophages Mice NF-kappa B Steroids Tumor Necrosis Factor-alpha Viral Envelope Proteins Human herpesvirus 1 Murinae Mus |
| spellingShingle |
Brassinosteroid HSV-1 IL-6 Immunomodulatory activity Murine herpetic stromal keratitis NF-κB TNF-α 3beta bromo 5alpha,22,23 trihydroxystigmastan 6 one brassinosteroid immunoglobulin enhancer binding protein interleukin 6 lipopolysaccharide tumor necrosis factor alpha unclassified drug animal cell antiviral activity article controlled study cornea cell cytokine production cytokine release herpes simplex keratitis Herpes simplex virus 1 human human cell immunomodulation immunostimulation immunosuppressive treatment macrophage mouse nonhuman Animals Antiviral Agents Cell Nucleus Cells, Cultured Cholestanones Epithelial Cells Epithelium, Corneal Gene Expression Regulation, Viral Herpesvirus 1, Human Humans Immunologic Factors Interleukin-6 Keratitis, Herpetic Macrophages Mice NF-kappa B Steroids Tumor Necrosis Factor-alpha Viral Envelope Proteins Human herpesvirus 1 Murinae Mus Michelini, F.M. Berra, A. Alché, L.E. The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice |
| topic_facet |
Brassinosteroid HSV-1 IL-6 Immunomodulatory activity Murine herpetic stromal keratitis NF-κB TNF-α 3beta bromo 5alpha,22,23 trihydroxystigmastan 6 one brassinosteroid immunoglobulin enhancer binding protein interleukin 6 lipopolysaccharide tumor necrosis factor alpha unclassified drug animal cell antiviral activity article controlled study cornea cell cytokine production cytokine release herpes simplex keratitis Herpes simplex virus 1 human human cell immunomodulation immunostimulation immunosuppressive treatment macrophage mouse nonhuman Animals Antiviral Agents Cell Nucleus Cells, Cultured Cholestanones Epithelial Cells Epithelium, Corneal Gene Expression Regulation, Viral Herpesvirus 1, Human Humans Immunologic Factors Interleukin-6 Keratitis, Herpetic Macrophages Mice NF-kappa B Steroids Tumor Necrosis Factor-alpha Viral Envelope Proteins Human herpesvirus 1 Murinae Mus |
| description |
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)-3β-bromo-5α,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-κB by inhibiting its translocation to the nucleus of infected corneal and conjunctival cells in vitro, as well as significantly reduced the secretion of TNF-α 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. © 2007 Elsevier Ltd. All rights reserved. |
| format |
JOUR |
| author |
Michelini, F.M. Berra, A. Alché, L.E. |
| author_facet |
Michelini, F.M. Berra, A. Alché, L.E. |
| author_sort |
Michelini, F.M. |
| title |
The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice |
| title_short |
The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice |
| title_full |
The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice |
| title_fullStr |
The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice |
| title_full_unstemmed |
The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice |
| title_sort |
in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice |
| url |
http://hdl.handle.net/20.500.12110/paper_09600760_v108_n1-2_p164_Michelini |
| work_keys_str_mv |
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1807323956827389952 |