Expression of urinary chemokines in patients with overactive bladder (OAB)
OBJECTIVES: Urine cytokine assays have been studied in various bladder and kidney disorders. Stretching of bladder wall as in filling may stimulate the urothelium to release Ach, ATP, nitros oxide and urothelial derived inhibition factor. One or more of these substances can activate sensory nerve endings in the lamina propria and urothelium where M2 and M3 receptors are present, leading to urgency. We hypothesize that overactive bladder can produce inflammatory cytokines as a result of afferent neural plasticity or from urothelial dysfunction. The objective of the present study was to detect abnormal cytokine levels in urine of patients with overactive bladder (OAB) compared to normal. METHODS: Prospective, single blind study including twenty healthy women (control) and 20 women suffering from overactive bladder (group II) were selected. Urine samples were collected, centrifuged, and mixed with protease inhibitor solution, pH 7.4 to prevent protein degradation, frozen, and stored at -80oC. Urinary total proteins were quantified using BCA protein micro assay kit in accord with manufacturer’s instructions. Differential expression profile analysis of cytokines in urine samples of normal and OAB were performed using a human cytokine protein chip. The levels of each cytokine were expressed and compared as mean +/- SE in normal subjects and OAB patients.
RESULTS: Amongst the expression of 120 cytokines studied in the present study, the majority of the cytokines showed same expression in the OAB as compared with the control. The chemokines which were found to have 2 fold or more positive expression were Monocyte chemoattractant protein 1 (MCP-1), Monocyte chemo-attractant protein 2 (MCP- 2), Monocyte chemo-attractant protein 3 (MCP-3), and Eotaxin-3. The proinflammoatry cytokines showing 2 fold or more positive expression were tumor necrosis factor beta (TNF), granulocyte colony stimulating factor (GCSF) and epidermal growth factor receptor (EGF-R). Few of the cytokines were down regulated like IL-5, IL-6, IL-7 and GM-CSF. It was striking to note that the expression of -Nerve growth factor (NGF) was low. CONCLUSIONS: These findings for the first time demonstrate that production of the most potent chemokine MCP-1 along with other chemokines and proinflammatory cytokines in patients with overactive bladder
The Journal of Urology
(2009). Expression of urinary chemokines in patients with overactive bladder (OAB). The Journal of Urology, 181, 574.
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