Nicotinic signaling ameliorates acute bladder inflammation induced by protamine sulfate or cyclophosphamide.
OBJECTIVE
Nicotinic afferent pathways may be involved in the regulation of bladder inflammation. Based on that hypothesis we investigated the role of nicotinic signaling in a comparative analysis of 2 models of experimental bladder inflammation using protamine sulfate and cyclophosphamide.


METHODS
Protamine sulfate and cyclophosphamide were used to induce acute bladder inflammation. Nicotinic agonists and antagonists were given concomitant to the bladder inflammatory agents. Changes in bladder inflammation were measured histologically by a pathologist and through the expression of inflammatory genes.


RESULTS
Histologically cyclophosphamide induced more inflammatory changes than protamine sulfate during acute bladder inflammation. Antagonizing nicotinic signaling with mecamylamine induced further inflammatory changes on histology when used with cyclophosphamide but not with protamine sulfate. However, antagonizing nicotinic signaling in combination with protamine sulfate induced greater increases in mRNA expression of the inflammatory cytokine interleukin-6 compared to cyclophosphamide and mecamylamine combination treatments. The activation of nicotinic signaling attenuated acute bladder inflammation by protamine sulfate and cyclophosphamide independently through the down-regulation of increased interleukin-6 expression.


CONCLUSIONS
Acutely cyclophosphamide treatment results in a greater frank bladder inflammation model in mice than protamine sulfate. However, cholinergic signaling can inhibit inflammation by either mechanism of induced bladder injury. Interleukin-6 gene expression is present and it can be regulated by afferent neuronal signaling even in the absence of observed histological changes in acute bladder inflammatory models.
Starkman
Jonathan S
JS
Department of Urologic Surgery, Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, Tennessee 37232-2765, USA.
Martinez-Ferrer
Magaly
M
Iturregui
Juan M
JM
Uwamariya
Consolate
C
Dmochowski
Roger R
RR
Bhowmick
Neil A
NA
D000208:Acute Disease; D000818:Animals; D003520:Cyclophosphamide / Q000008:administration & dosage; D003556:Cystitis / Q000139:chemically induced / Q000503:physiopathology* / Q000517:prevention & control; D004195:Disease Models, Animal; D051379:Mice; D008810:Mice, Inbred C57BL; D011479:Protamines / Q000008:administration & dosage; D011978:Receptors, Nicotinic / Q000502:physiology*
D011479:Protamines; D011978:Receptors, Nicotinic; D003520:Cyclophosphamide