The function and mechanism of NALP3 inflammasome in interstitial cystitis/bladder pain syndrome

Abstract

Objective To acknowledge the NALP3 inflammasome expression and significance in the interstitial cystitis/bladder pain syndrome (IC/PBS). Methods The urine of 16 IC/BPS patients and 16 normal persons was collected to measure the IL-1β content by ELISA. Bladder tissue of 16 IC/BPS patients and para-carcinoma tissue of 16 bladder cancer patients were collected. And the levels of NALP3, caspase-1 and IL-1β were detected by Western Blot. 60 female rats were randomly divided into control group(bladder was infused with 0.5 ml saline), hyaluronidase group[bladder was infused with 0.5 ml hyaluronidase(4 mg/ml)] , NALP3 antagonist group[bladder was infused with 0.5 ml hyaluronidase(4 mg/ml) and Glyburide(10 mg/kg)] and mucosal protectant group [bladder was infused with 0.5 ml hyaluronidase (4 mg/ml) and sodium hyaluronate(0.8 mg/ml)] to carried out the animal experiment, and 15 rats in each group. The models were created by long-term (1 month) intermittent intravesical hyaluronidase infusion. Voiding patterns were investigated by cystometry. Toluidine blue staining was used to detected mast cell's changes. The levels of NALP3 , caspase-1 and IL-1β were determined by Western Blot, HE staining was to detect tissue inflammation of the bladder, and the severity of pain was examined by Von-frey brush by using the strength of 0.07、0.4、1.0 g. The comparison between the chemotaxis of 200 ng, 400 ng IL-1β and 200ng SCF IL-1β to mast cells was checked by Transwell experiment. Results The expressions of IL-1β in IC/PBS patients was increased in IC/PBS group than normal control group [(381±112)μg/L vs. (98±40)μg/L, P 0.05). Conclusions The levels of NALP3/Caspase-1/IL-1β in the urine of patients with IC/PBS were significantly higher than those in normal control group. NALP3 is activated in chronic cystitis rat model , and related to pain and frequent urination. This may be related to the down-regulation of expression of NALP3, caspase-1, IL-1β, and other inflammatory mediators, and blocking the chemotactic effects of IL-1β on mast cells. Key words: Interstitial cystitis/bladder pain syndrome; NALP3 protein; Interleukin-1β