Abstract Book - 26th ESPU Congress, Joint Meeting with ICCS + SPU + AAP/SOU + AAPU + SFU

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13:33 - 13:36
S1-2 (PP)
IL-33 MAST CELL AXIS IN BLADDER INFLAMMATION AND PAIN
Siam OOTTAMASATHIEN1, Wanjian JIA1, Austin SCHULTS1, Xiangyang YE2, Laura SPRINGHETTI1, Jeremiah ALT3 and
Glenn PRESTWICH4
1) University of Utah, Pediatric Urology, Salt Lake City, USA - 2) University of Utah, Biostatistics, Salt Lake City, USA -
3) University of Utah, Otolaryngology, Salt Lake City, USA - 4) University of Utah, Medicinal Chemistry, Salt Lake City,
USA
PURPOSE
We've previously demonstrated the naturally occurring urinary anti-microbial peptide LL-37 can induce bladder
inflammation and pain. Our aim was to establish a molecular and cellular axis by which this occurs. We first
hypothesized that IL-33 is upregulated in LL-37 induced bladder injury. We further hypothesized that both bladder
inflammation and pain, along with IL-33 levels, are attenuated in mast cell deficient mice (C-kit(-/-)).
MATERIAL AND METHODS
To test hypothesis one, C57Bl/6 mice bladders were challenged with LL-37 for 1hr (six concentrations). Controls
consisted of saline. Bladders were harvested after 24hrs. Both immunohistochemistry (IHC) and quantitative ELISAs
were performed to detect IL-33. For hypothesis two, both C-kit(-/-) and normal C57Bl/6 mice (controls) were challenged
with four concentrations of LL-37. Pain responses with von-Frey filaments were performed before LL-37 instillation and
after 24hrs. Bladders were obtained after 24hrs, evaluated with histology, tissue myeloperoxidase (MPO), and IL-33
ELISA's.
RESULTS
IHC revealed no evidence of IL-33 in controls. In LL-37 challenged tissues, IL-33 was observed in urothelium and
fibroblasts. ELISAs for IL-33 levels in LL-37 challenged tissues demonstrated a dose response rise. Histologically, C-kit(-
/-) bladders were less inflamed compared to normals. Quantifying inflammation with MPO confirmed significantly less
inflammation within C-kit(-/-). Pain responses were also significantly less in C-kit(-/-). Substantial differences in IL-33
levels were observed at higher concentrations of LL-37 challenge (C-kit(-/-):567 pg/ml vs. normal:972 pg/ml).
CONCLUSIONS
Our findings demonstrate a novel inflammatory and pain axis, implicating IL-33 and mast cells. Future therapeutics
aimed at targeting the IL-33 mast cell axis may serve as useful treatment approaches.