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Activation of Toll‐like receptor 4 mediates bladder hypercontractility in diabetes (865.10)
Author(s) -
Szasz Theodora,
Nunes Kenia P.,
Webb R. Clinton
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.865.10
Subject(s) - tlr4 , urothelium , carbachol , medicine , diabetes mellitus , contraction (grammar) , streptozotocin , inflammation , receptor , urinary bladder , endocrinology , toll like receptor , urology , innate immune system
Diabetic bladder dysfunction (DBD) is a common lower urinary tract complication of diabetes. Manifestations of DBD progress from bladder hypercontractility and urge incontinence in the initial phase to bladder hypocontractility and overflow incontinence in the late phase. Activation of the innate immune system via Toll‐like receptors (TLRs) like TLR4 leads to inflammation and oxidative stress and was implicated in diabetes pathophysiology. We hypothesized that bladder hypercontractility in the initial phase of DBD is mediated by TLR4 activation. Urinary bladder strips without urothelium from male C57bl/6 mice treated with vehicle or streptozotocin (65 mg/kg twice) were used to evaluate contractile function and protein expression of TLR4 and downstream mediator MyD88. Bladder expression of TLR4 and MyD88 was increased in STZ compared to control mice (TLR4=178±26, MyD88=138±12 % control). Carbachol‐mediated contraction was increased in bladder strips from STZ mice. The TLR4 inhibitor CLI095 (10 μM) decreased the maximal CCh‐induced contraction in STZ, but not in control mice (CON= 67.6±2.3, STZ=93.7±11.6, CON+CLI=76.3±6.7, STZ+CLI=66.2±7.2 % KCl‐induced contraction). These data suggest that activation of TLR4 during diabetes mediates bladder hypercontractility and contributes to DBD. Grant Funding Source : NIH