The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice

Michelini, Flavia; Berra, Alejandro; Alché, Laura E.

doi:10.1016/j.jsbmb.2007.10.002

Cited by 29 publications

(66 citation statements)

References 21 publications

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“…An in vivo study of the antiherpetic properties of 25 in the murine stromal keratin experimental model led to the conclusion that the compound did not exert a direct antiviral effect [144]. Instead, it acted as an inductor or an inhibitor of cytokine production, thus modulating the response of epithelial and immune cells to herpes virus infection [150]. The protective effect in mice was explained as a balance between immunostimulatory and immunosuppressive effects of 25.…”

Section: Antiviral Effectsmentioning

confidence: 99%

Steroid plant hormones: Effects outside plant kingdom

2015

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Section: Antiviral Effectsmentioning

confidence: 99%

Steroid plant hormones: Effects outside plant kingdom

2015

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“…Several reports sourced mainly from the Laboratory of Virology at the University of Buenos Aires, Argentina, have concluded that synthetic analogs of BR have potent antiviral activities against animal viruses such as herpes simplex virus type 1, vesicular stomatitis virus, junin virus, and measles virus [62][63][64][65]. Time-related experiments have shown that synthetic BRs can inhibit, depending on the virus, either an early event or a late event of virus growth.…”

Section: Anticancer and Antiviral Effectsmentioning

confidence: 99%

“…Time-related experiments have shown that synthetic BRs can inhibit, depending on the virus, either an early event or a late event of virus growth. A synthetic BR was also demonstrated to exert immunomodulatory activities, such as enhanced production of interleukin-6 that acts as both a proinflammatory and anti-inflammatory cytokine, and blockage of virus-induced activation of nuclear factor-kB in virus infected cells [62]. A recent report from the Palacky University in the Czech Republic makes the intriguing observation that natural BRs, such as EBR and 28-homocastasterone, have anticancer and antiproliferative activities [66].…”

Section: Anticancer and Antiviral Effectsmentioning

confidence: 99%

Brassinosteroids Confer Stress Tolerance

Divi¹,

Krishna²

2009

Plant Stress Biology

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IntroductionBrassinosteroids (BRs) are a group of plant steroidal hormones that are structurally related to animal and insect steroid hormones. BRs regulate a wide range of physiological responses in plants, including cell elongation, photomorphogenesis, xylem differentiation, seed germination [1], and stress responses [2,3]. Although the growth-promoting properties of BRs were recognized in the early 1970s, the first genetic evidence to suggest that BRs are essential for proper plant development came with the isolation of the BR-deficient mutants det2 (de-etiolated2) and cpd (constitutive photomorphogenic dwarf ) [4,5]. Isolation and sequence analysis of DET2 and CPD genes revealed that the encoded proteins share sequence similarities with steroid 5a-reductases and steroid hydroxylases, respectively, indicating a role for these proteins in steroid metabolism. Indeed, feeding det2 and cpd mutant seedlings with BRs rescued their mutant phenotypes to wild-type in a dose-dependent manner, clearly establishing the roles of DET2 and CPD in BR biosynthesis. Numerous other Arabidopsis BR-deficient and BR-insensitive mutants, displaying phenotypic alterations such as dwarfism, small dark-green leaves, a compact rosette structure, delayed flowering and senescence, and reduced fertility [1], were instrumental in the identification of BR signaling components and in understanding to some extent how BR regulates gene expression [6,7]. Numerous reviews detailing BR effects on plant growth and development and BR signaling mechanisms have surfaced in the recent literature [6-10]; these aspects have therefore been discussed only briefly here. The present chapter is focused on the relatively less explored topic of BR-mediated stress responses in plants [3] and highlights the progress made towards understanding the molecular basis of BRmediated plant stress tolerance.Plant Stress Biology. Edited by H. Hirt BR is perceived at the cell surface by BRI1 (BR-INSENSITIVE1), a plasma membrane-localized leucine-rich repeat (LRR) receptor-like kinase (RLK) [11,12]. BR binding to BRI1 induces a series of biochemical events, such as autophosphorylation of BRI1 in its C-terminal domain, dissociation of an inhibitory protein, BKI1 (BRI1 KINASE INHIBITOR1), and association of BRI1 with another LRR RLK, BAK1 (BRI1-ASSOCIATED RECEPTOR KINASE1) [13,14]. The recent demonstration that BR-dependent activation of BRI1 precedes association with BAK1 has led to a model in which BAK1 enhances signaling output through reciprocal BRI1 transphosphorylation [15]. However, whether the main function of BAK1 is to enhance signaling output of BRI1, promote endocytosis of BRI1, or to help link BRI1 with a downstream signaling protein remains to be determined [7]. Other known components of the BR signaling pathway include GSK3 (GLYCO-GEN SYNTHASE KINASE3), BIN2 (BR-INSENSITIVE2), which negatively regulates the transcription factors BZR1 (BRASSINAZOLE-RESISTANT1) and BES1 (BRI1-EMS SUPPRESSOR1) by phosphorylating them [16,17], while the phosphatase BSU1 (BRI1 SUPPRE...

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“…Despite the lack of anti-HSV activity of this compound in vivo conditions, it significantly decreases the incidence of HSK in the murine model of HSV-1 corneal infection, probably due to an immunomodulatory effect [8]. Furthermore, this stigmastane derivative inhibits the production of TNF-␣ in a LPS-stimulated murine macrophage cell line [9,10], and modulates the secretion of IL-6 and TNF-␣ in human epithelial cells derived from ocular tissues [9].…”

Section: Introductionmentioning

confidence: 99%

Anti-herpetic and anti-inflammatory activities of two new synthetic 22,23-dihydroxylated stigmastane derivatives

Michelini

Ramírez

Berra

et al. 2008

The Journal of Steroid Biochemistry and Molecular Biology

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Stromal keratitis resulting from ocular infection with Herpes simplex virus type 1 (HSV-1) is a common cause of blindness. This report investigates the antiviral and anti-inflammatory properties of two new synthetic stigmastane analogs in the experimental model of HSV-1-induced ocular disease in mice. (22S,23S)-22,23-dihydroxystigmast-4-en-3-one (1) and (22S,23S)-22,23-dihydroxystigmasta-1,4-dien-3-one (2) exhibited anti-HSV-1 activity in vitro and ameliorated the signs of murine herpetic stromal keratitis (HSK), although none of the compounds showed antiviral activity in vivo. We discuss that the improvement of HSK could be due to an immunomodulatory effect of both compounds.

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The in vitro immunomodulatory activity of a synthetic brassinosteroid analogue would account for the improvement of herpetic stromal keratitis in mice

Cited by 29 publications

References 21 publications

Steroid plant hormones: Effects outside plant kingdom

Steroid plant hormones: Effects outside plant kingdom

Brassinosteroids Confer Stress Tolerance

Anti-herpetic and anti-inflammatory activities of two new synthetic 22,23-dihydroxylated stigmastane derivatives

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