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Mast cell regulation of inflammation and gene expression during antigen-induced bladder inflammation in mice

¹ Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104
² Tulane Environmental Astrobiology Center, and Nephrology Section, Tulane University Medical Center, and Veterans Affairs Medical Center, New Orleans, Louisiana 70112
³ Departments of Pediatrics, Microbiology and Immunology, State University of New York Downstate Medical Center, Brooklyn, New York 11203-2098

Mast cell numbers are significantly increased in bladder disorders including malignancy and interstitial cystitis, but their precise role has been difficult to determine. We characterized the role of mast cells on gene regulation associated with antigen-induced bladder inflammation in mice. For this purpose, we examined the responses in mast cell-deficient (Kit^W/Kit^W-v), congenic normal (+/+), and Kit^W/Kit^W-v mice that were reconstituted with bone marrow stem cells (BMR) to restore mast cells. All mice were actively sensitized and challenged intravesically with either saline or specific antigen. Bladder inflammation occurred in +/+ and BMR but not the Kit^W/Kit^W-v mice. Gene expression was determined using mouse cDNA expression arrays. Self-organizing maps, performed without preconditions, indicated gene expression changes dependent on the presence of mast cells. These genes were upregulated in bladders isolated from antigen challenge of +/+, not altered in Kit^W/Kit^W-v, and were upregulated in BMR mice. Taken together these results demonstrate an important role for mast cells in allergic cystitis and indicate that mast cells can alter their environment by regulating tissue gene expression.

self-organizing maps; gene array; mast cell-deficient mice; inflammation; mast cells; and interstitial cystitis