OBJECTIVE: To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant. MATERIALS AND METHODS: We devised a mouse model of allergen-induced allergic cystitis that is associated with the up-regulation of genes for interleukin-13, FcepsilonRIalpha and mast cells-derived proteases, a massive inflammatory reaction in the bladder tissue, and augmented levels of mast cell-derived protease 1 (MMCP1) detected in mouse sera. RESULTS: Oral administration of BXL628 significantly reduced the expression of interleukin-13, FcepsilonRIalpha and MMCP1 in the bladder. Furthermore, histological analysis showed a decrease in oedema and leukocyte infiltration in the bladder wall. BXL628 treatment reduced serum MMCP1 levels, indicating an effect on mast cell degranulation in vivo. CONCLUSIONS: Vitamin D3 analogues may successfully be used as anti-inflammatory agents in allergen-mediated inflammatory reactions. Moreover, the modulatory effect shown on mast cell activation by the BXL628 analogue strongly supports its potential therapeutic use in a possibly mast cell-dependent disease such as human interstitial cystitis.
OBJECTIVE: To investigate the effects of a vitamin D3 analogue (BXL628) in a model of chronic cystitis, as calcitriol analogues might be an interesting new therapeutic option for interstitial cystitis, for although the cause of the disease remains unclear, the increase in mast cells in the mucosa and detrusor muscle are significant. MATERIALS AND METHODS: We devised a mouse model of allergen-induced allergic cystitis that is associated with the up-regulation of genes for interleukin-13, FcepsilonRIalpha and mast cells-derived proteases, a massive inflammatory reaction in the bladder tissue, and augmented levels of mast cell-derived protease 1 (MMCP1) detected in mouse sera. RESULTS: Oral administration of BXL628 significantly reduced the expression of interleukin-13, FcepsilonRIalpha and MMCP1 in the bladder. Furthermore, histological analysis showed a decrease in oedema and leukocyte infiltration in the bladder wall. BXL628 treatment reduced serum MMCP1 levels, indicating an effect on mast cell degranulation in vivo. CONCLUSIONS:Vitamin D3 analogues may successfully be used as anti-inflammatory agents in allergen-mediated inflammatory reactions. Moreover, the modulatory effect shown on mast cell activation by the BXL628 analogue strongly supports its potential therapeutic use in a possibly mast cell-dependent disease such as humaninterstitial cystitis.
Authors: Mehmet Yasar Ozkars; Ozlem Keskin; Mehmet Almacioglu; Ercan Kucukosmanoglu; Mehmet Keskin; Onur Balci Journal: North Clin Istanb Date: 2019-07-04