Mast cells mediate substance P-induced bladder inflammation through an NK(1) receptor-independent mechanism.
The role of neurokinin-1 receptors (NK1R) in the interaction between mast cells and substance P (SP) in bladder inflammation was determined. Mast cell-deficient Kit(W)/Kit(W-v), congenic normal (+/+), and Kit(W)/Kit(W-v) mice 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 NK1R expression on the mast cell. Cluster analysis identified functionally significant genes that were dependent on the presence of mast cells for their upregulation regardless of stimulus. Those include serine protein inhibitor 2.2, maspin, mitogen- and stress-activated protein kinase 2, and macrophage colony-stimulating factor 1. 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. When combined with unique animal models, gene array analysis provides a useful approach for identifying and characterizing pathways involved in bladder inflammation.
Saban
Ricardo
R
Department of Physiology, University of Oklahoma Health Sciences Center, Oklahoma City 73190, USA. ricardo-saban@ouhsc.edu
Gerard
Norma P
NP
Saban
Marcia R
MR
Nguyen
Ngoc-Bich
NB
DeBoer
Douglas J
DJ
Wershil
Barry K
BK
D000818:Animals; D002452:Cell Count; D003556:Cystitis / Q000139:chemically induced* / Q000473:pathology*; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D008407:Mast Cells / Q000473:pathology*; D051379:Mice; D018345:Mice, Knockout; D005810:Multigene Family; D020411:Oligonucleotide Array Sequence Analysis; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D018040:Receptors, Neurokinin-1 / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D015203:Reproducibility of Results; D013373:Substance P; D001743:Urinary Bladder / Q000473:pathology*
D018076:DNA, Complementary; D018040:Receptors, Neurokinin-1; D013373:Substance P; D019009:Proto-Oncogene Proteins c-kit