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

Mast cell numbers are significantly increased in bladder disorders includin g malignancy and interstitial cystitis, but their precise role has been dif ficult to determine. We characterized the role of mast cells on gene regula tion 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 acti vely sensitized and challenged intravesically with either saline or specifi c antigen. Bladder inflammation occurred in +/+ and BMR but not the Kit(W)/ Kit(W-v) mice. Gene expression was determined using mouse cDNA expression a rrays. Self-organizing maps, performed without preconditions, indicated gen e expression changes dependent on the presence of mast cells. These genes w ere upregulated in bladders isolated from antigen challenge of +/+, not alt ered in Kit(W)/Kit(W-v), and were upregulated in BMR mice. Taken together t hese results demonstrate an important role for mast cells in allergic cysti tis and indicate that mast cells can alter their environment by regulating tissue gene expression.