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Am J Physiol Renal Physiol (May 22, 2002). doi:10.1152/ajprenal.00096.2002
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Articles in PresS, published online ahead of print May 22, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00096.2002
Submitted on March 12, 2002
Accepted on May 9, 2002

Mast cells mediate substance P-induced bladder inflammation through a neurokinin-1 receptor-independent mechanism

Ricardo Saban1*, Norma P Gerard2, Marcia R Saban1, Ngoc-Bich Nguyen1, Douglas J DeBoer3, and Barry K Wershil4

1 Physiology, OUHSC, Oklahoma City, OK, USA
2 Pulmonary Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Ina Sue Pelmutter Laboratory, Children's Hospital, Harvard Medical School, Boston, MA, USA
3 Department of Medical Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI, USA
4 Department of Pediatrics, Health Science Center at Brooklyn, State University of New York, Brooklyn, NY, USA

* To whom correspondence should be addressed. E-mail: ricardo-saban{at}ouhsc.edu.

The role of neurokinin-1 receptors (NK-1R) in the interaction between mast cells and substance P (SP) in bladder inflammation was determined. Mast cell-deficient KitW/KitW-v, congenic normal (+/+), and KitW/KitW-v that were reconstituted with bone marrow cells isolated from NK1R-/- mice were challenged by instillation of SP, antigen, or saline into the urinary bladder. Twenty-four hours after challenge, the bladders were prepared for morphological assessment and gene expression. SP-induced bladder inflammation was mast cell-dependent and did not require NK-1R expression on the mast cell. Cluster analysis identified functionally significant genes that were dependent on the presence of mast cells for their up-regulation regardless of stimulus. Those include: Spi 2.2, maspin, mitogen- and stress-activated protein kinase 2, and MCP1. Our findings demonstrate that while mast cells are essential for both antigen- and SP-induced bladder inflammation, there are common genes and unique genes expressed in each type of inflammatory reaction. Gene array analysis provides a useful approach for identifying and characterizing pathways involved in bladder inflammation when combined with unique animal models.




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