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Inflammation Research

, Volume 65, Issue 9, pp 737–743 | Cite as

VBP15, a novel dissociative steroid compound, reduces NFκB-induced expression of inflammatory cytokines in vitro and symptoms of murine trinitrobenzene sulfonic acid-induced colitis

  • Jesse M. DamskerEmail author
  • Laurie S. Conklin
  • Soheil Sadri
  • Blythe C. Dillingham
  • Karuna Panchapakesan
  • Christopher R. Heier
  • John M. McCall
  • Anthony D. Sandler
Original Research Paper

Abstract

Objective and design

The goal of this study was to assess the capacity of VBP15, a dissociative steroidal compound, to reduce pro-inflammatory cytokine expression in vitro, to reduce symptoms of colitis in the trinitrobenzene sulfonic acid-induced murine model, and to assess the effect of VBP15 on growth stunting in juvenile mice.

Materials

In vitro studies were performed in primary human intestinal epithelial cells. Colitis was induced in mice by administering trinitrobenzene sulfonic acid. Growth stunting studies were performed in wild type outbred mice.

Treatment

Cells were treated with VBP15 or prednisolone (10 μM) for 24 h. Mice were subjected to 3 days of VBP15 (30 mg/kg) or prednisolone (30 mg/kg) in the colitis study. In the growth stunting study, mice were subjected to VBP15 (10, 30, 45 mg/kg) or prednisolone (10 mg/kg) for 5 weeks.

Methods

Cytokines were measured by PCR and via Luminex. Colitis symptoms were evaluated by assessing weight loss, intestinal blood, and stool consistency. Growth stunting was assessed using an electronic caliper.

Results

VBP15 significantly reduced the in vitro production of CCL5 (p < 0.001) IL-6 (p < 0.001), IL-8 (p < 0.05) and reduced colitis symptoms (p < 0.05). VBP15 caused less growth stunting than prednisolone (p < 0.001) in juvenile mice.

Conclusion

VBP15 may reduce symptoms of IBD, while decreasing or avoiding detrimental side effects.

Keywords

Inflammation Autoimmunity Glucocorticoids Inflammatory bowel disease 

Notes

Compliance with ethical standards

Conflict of interest

Dr. Jesse Damsker and Dr. John McCall are employed by ReveraGen BioPharma Inc. and have stock options and founder shares, respectively.

Financial support

Supported by ReveraGen BioPharma Inc. Sheikh Zayed Institute for Pediatric Surgical Innovation, NIH Grant (1R41DK102235-01).

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Copyright information

© Springer International Publishing 2016

Authors and Affiliations

  • Jesse M. Damsker
    • 1
    Email author
  • Laurie S. Conklin
    • 2
    • 3
  • Soheil Sadri
    • 2
    • 3
  • Blythe C. Dillingham
    • 4
  • Karuna Panchapakesan
    • 4
  • Christopher R. Heier
    • 4
  • John M. McCall
    • 1
    • 5
  • Anthony D. Sandler
    • 2
    • 3
  1. 1.ReveraGen BioPharma Inc.RockvilleUSA
  2. 2.The Joseph E. Robert Center for Surgical CareChildren’s National Health SystemWashington, DCUSA
  3. 3.The Sheikh Zayed Institute for Pediatric Surgical InnovationChildren’s National Health SystemWashington, DCUSA
  4. 4.Research Center for Genetic MedicineChildren’s National Health SystemWashington, DCUSA
  5. 5.PharMac LLCBoca GrandeUSA

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