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 signal...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology. Renal physiology 2009-10, Vol.297 (4), p.F1038-F1044
Main Authors: Cheppudira, Bopaiah P, Girard, Beatrice M, Malley, Susan E, Dattilio, Abbey, Schutz, Kristin C, May, Victor, Vizzard, Margaret A
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents, Alkylating
Bladder
Cyclophosphamide
Cystitis - chemically induced
Cystitis - metabolism
Cytokines
Female
Janus Kinase 2 - antagonists & inhibitors
Janus Kinase 2 - metabolism
Kidneys
Phosphorylation
Rats
Rats, Wistar
Rodents
Signal Transduction
STAT3 Transcription Factor - metabolism
Stress, Physiological
Studies
Tyrphostins
Urinary Bladder - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00110.2009