Involvement of JAK-STAT signaling/function after cyclophosphamide-induced bladder inflammation in female rats.
Cytokines are upregulated in a variety of inflammatory conditions and cytokine/receptor interactions can activate JAK-STAT signaling. Previous studies demonstrated upregulation of numerous cytokines in the urinary bladder following cyclophosphamide (CYP)-induced cystitis. The role of JAK-STAT signaling in urinary bladder inflammation and referred somatic sensitivity has not been addressed. The contribution of JAK-STAT signaling pathways in CYP-induced bladder hyperreflexia and referred somatic hypersensitivity was determined in CYP-treated rats using a JAK2 inhibitor, AG490. Acute (4 h; 150 mg/kg ip), intermediate (48 h; 150 mg/kg ip), or chronic (75 mg/kg ip, once every 3 days for 10 days) cystitis was induced in adult, female Wistar rats with CYP treatment. Phosphorylation status of STAT-3 was increased in urinary bladder after CYP-induced cystitis (4 h, 48 h, chronic). Blockade of JAK2 with AG490 (5-15 mg/kg ip or intravesical) significantly (P < or = 0.05) reduced bladder hyperreflexia and hind paw sensitivity in CYP-treated rats. These studies demonstrate a potential role for JAK-STAT signaling pathways in bladder hyperreflexia and referred pain induced by CYP-induced bladder inflammation.
Cheppudira
Bopaiah P
BP
Dept. of Neurology, Univ. of Vermont College of Medicine, Burlington, VT 05405, USA.
Girard
Beatrice M
BM
Malley
Susan E
SE
Dattilio
Abbey
A
Schutz
Kristin C
KC
May
Victor
V
Vizzard
Margaret A
MA
D000818:Animals; D018906:Antineoplastic Agents, Alkylating; D003520:Cyclophosphamide; D003556:Cystitis / Q000139:chemically induced / Q000378:metabolism*; D005260:Female; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D013312:Stress, Physiological; D020032:Tyrphostins; D001743:Urinary Bladder / Q000378:metabolism*
D018906:Antineoplastic Agents, Alkylating; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D003520:Cyclophosphamide; C507927:Jak2 protein, rat; D053614:Janus Kinase 2