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) α, 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-6Rα, 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.