期刊
FRONTIERS IN NEUROSCIENCE
卷 5, 期 -, 页码 -出版社
FRONTIERS RESEARCH FOUNDATION
DOI: 10.3389/fnins.2011.00020
关键词
urothelium; detrusor smooth muscle; Q-PCR; Western blotting; gp130; LIF
资金
- VT Cancer Center DNA Analysis Facility
- Department of Pharmacology, University of Illinois at Chicago, Chicago, USA [IL 60612]
- NIH [DK051369, DK060481, DK065989]
- NIH from COBRE Program of the National Center [P20 RR16435]
- NATIONAL CENTER FOR RESEARCH RESOURCES [P20RR016435] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK060481, R01DK051369, R56DK060481, R01DK065989, R29DK051369] Funding Source: NIH RePORTER
Recent studies suggest that janus-activated kinases-signal transducer and activator of transcription signaling pathways contribute to increased voiding frequency and referred pain of cyclophosphamide (CYP)-induced cystitis in rats. Potential upstream chemical mediator(s) that may be activated by CYP-induced cystitis to stimulate JAK/STAT signaling are not known in detail. In these studies, members of the interleukin (IL)-6 family of cytokines including, leukemia inhibitory factor (LIF), IL-6, and ciliary neurotrophic factor (CNTF) and associated receptors, IL-6 receptor (R) alpha, LIFR, and gp130 were examined in the urinary bladder in control and CYP-treated rats. Cytokine and receptor transcript and protein expression and distribution were determined in urinary bladder after CYP-induced cystitis using quantitative, real-time polymerase chain reaction (Q-PCR), western blotting, and immunohistochemistry. Acute (4 h; 150 mg/kg; i.p.), intermediate (48 h; 150 mg/kg; i.p.), or chronic (75 mg/kg; i.p., once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Q-PCR analyses revealed significant (p <= 0.01) CYP duration- and tissue- (e.g., urothelium, detrusor) dependent increases in LIF, IL-6, IL-6R alpha, LIFR, and gp130 mRNA expression. Western blotting demonstrated significant (p <= 0.01) increases in IL-6, LIF, and gp130 protein expression in whole urinary bladder with CYP treatment. CYP-induced cystitis significantly (p <= 0.01) increased LIF-immunoreactivity (IR) in urothelium, detrusor, and suburothelial plexus whereas increased gp130-IR was only observed in urothelium and detrusor. These studies suggest that IL-6 and LIF may be potential upstream chemical mediators that activate JAK/STAT signaling in urinary bladder pathways.
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