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Role of nicotinic and estrogen signaling during experimental acute and chronic bladder inflammation.

Martinez-Ferrer M, Iturregui JM, Uwamariya C, Starkman J, Sharif-Afshar AR, Suzuki K, Visedsindh W, Matusik RJ, Dmochowski RR, Bhowmick NA
Am J Pathol. 2008 172 (1): 59-67

PMID: 18079438 · PMCID: PMC2189612 · DOI:10.2353/ajpath.2008.070529

Inflammation is a physiological process that characterizes many bladder diseases. We hypothesized that nicotinic and estrogen signaling could down-regulate bladder inflammation. Cyclophosphamide was used to induce acute and chronic bladder inflammation. Changes in bladder inflammation were measured histologically and by inflammatory gene expression. Antagonizing nicotinic signaling with mecamylamine further aggravated acute and chronic inflammatory changes resulting from cyclophosphamide treatment. Estrogen and nicotinic signaling independently attenuated acute bladder inflammation by decreasing neutrophil recruitment and down-regulating elevated lipocalin-2 and cathepsin D expression. However, the combined signaling by the estrogen and nicotinic pathways, as measured by macrophage infiltration and up-regulation of interleukin-6 expression in the bladder, synergistically reduced chronic bladder inflammation. The elevated expression of p65 nuclear localization in bladders treated with cyclophosphamide or cyclophosphamide with mecamylamine suggested nuclear factor-kappa B activation in the chronic inflammatory process. The complementary treatment of 17 beta-estradiol and the nicotinic agonist anabasine resulted in the translocation of p65 to the cytoplasm, again greater than either alone. Activation of nuclear factor-kappaB can result in macrophage activation and/or elevation in epithelial proliferation. These data suggest that 17 beta-estradiol and anabasine reduce chronic bladder inflammation through reduction of nuclear translocation of p65 to suppress cytokine expression.

MeSH Terms (15)

Animals Antineoplastic Agents, Alkylating Cell Nucleus Cyclophosphamide Cystitis Estradiol Female Gene Expression Regulation Inflammation Mecamylamine Mice Mice, Inbred C57BL Receptors, Nicotinic Signal Transduction Urinary Bladder

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