Nuclear factor kappa B mediates lipopolysaccharide-induced inflammation in the urinary bladder

被引:33
作者
Wang, XC
Saban, R
Kaysen, JH
Saban, MR
Allen, PL
Benes, EN
Hammond, TG
机构
[1] Tulane Univ, Sch Med, Nephrol Sect SL45,Ctr Bioenvironm Res, Ctr Med,Tulane Environm Astrobiol Ctr, New Orleans, LA 70112 USA
[2] Vet Adm Med Ctr, New Orleans, LA 70146 USA
[3] Univ Texas, Med Branch, Div Gastroenterol, Enteric Neuromuscular Dis Lab, Galveston, TX 77550 USA
关键词
inflammation; urinary bladder; transcription factor; NF-kappa B;
D O I
10.1016/S0022-5347(05)67870-6
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Purpose: The proteins which constitute the final common pathway linking receptors on cell surfaces to the inflammatory cascade have recently,been identified and cloned. Central to activation of this inflammatory cascade is translocation from cytosol to nucleus of the nuclear transcription factor known as nuclear factor-kappa B (NF-kappa B). The purpose of this study was to determine whether NF-kappa B cascade plays a role in lipopolysaccharide (LPS)-induced inflammation of the mouse urinary bladder. Materials and Methods: Bladder inflammation was induced in anesthetized mice by intravesical instillation of lipopolysaccharide (LPS) and quantified by morphometric analysis. The NK-1 receptors for substance P were quantified by flow cytometry. LPS-induced degradation of inhibitory I kappa B subunit was quantified by Western blotting analysis and translocation of NF-kappa B protein from cytosol to the nucleus was determined by confocal microscopy and Western blotting analysis. In addition, we determine the effect of lactacystin, a proteosome inhibitor, on LPS-induced I kappa B degradation and NF-kappa B translocation, NK-1 receptor fluorescence intensity, and bladder inflammation. Results: LPS instillation into the mouse bladder resulted in time dependent loss of the inhibitory I kappa B subunit of the NF-kappa B protein complex. I kappa B cleavage was followed by translocation of NF-kappa B from the cytosol to the nucleus. This was associated with increased expression of an NF-kappa B dependent inflammatory component, the NK-1 receptor. Pretreatment of mouse bladders with the NF-kappa B inhibitor, lactacystin, prevented cleavage of I kappa B in a dose-dependent manner. Lactacystin prevented increases in the NF-kappa B dependent inflammatory cascade components such as the NK-1 receptor. At the whole tissue level, the marked inflammatory infiltrate and mucosal breakdown associated with LPS administration was completely abolished by lactacystin. Conclusion: NF-kappa B mediates many features of urinary bladder inflammation induced by LPS. The NF-kappa B cascade is an important target for anti-inflammatory management of cystitis,
引用
收藏
页码:993 / 998
页数:6
相关论文
共 37 条
[1]   Potential role of rel/nuclear factor-κb in the pathogenesis of interstitial cystitis [J].
Abdel-Mageed, AB ;
Ghoniem, GM .
JOURNAL OF UROLOGY, 1998, 160 (06) :2000-2003
[2]   CHARACTERIZATION OF THE CAPSAICIN-SENSITIVE COMPONENT OF CYCLOPHOSPHAMIDE-INDUCED INFLAMMATION IN THE RAT URINARY-BLADDER [J].
AHLUWALIA, A ;
MAGGI, CA ;
SANTICIOLI, P ;
LECCI, A ;
GIULIANI, S .
BRITISH JOURNAL OF PHARMACOLOGY, 1994, 111 (04) :1017-1022
[3]   ENDOTOXIN-INDUCED SHEDDING OF VIABLE UROEPITHELIAL CELLS IS AN ANTIMICROBIAL DEFENSE-MECHANISM [J].
ARONSON, M ;
MEDALIA, O ;
AMICHAY, D ;
NATIV, O .
INFECTION AND IMMUNITY, 1988, 56 (06) :1615-1617
[4]   The NF-kappa B and I kappa B proteins: New discoveries and insights [J].
Baldwin, AS .
ANNUAL REVIEW OF IMMUNOLOGY, 1996, 14 :649-683
[5]   NF-kappa B: A pivotal role in asthma and a new target for therapy [J].
Barnes, PJ ;
Adcock, IM .
TRENDS IN PHARMACOLOGICAL SCIENCES, 1997, 18 (02) :46-50
[6]   NEUROGENIC INFLAMMATION OF GUINEA-PIG BLADDER [J].
BJORLING, DE ;
SABAN, MR ;
SABAN, R .
MEDIATORS OF INFLAMMATION, 1994, 3 (03) :189-197
[7]   Lipopolysaccharide upregulates bradykinin 1 receptors in the isolated mouse bladder [J].
Busser, BW ;
Hammond, TG ;
Bjorling, DE ;
Saban, R .
JOURNAL OF UROLOGY, 1998, 160 (06) :2267-2273
[8]   PERMEABILITY PROPERTIES OF THE MAMMALIAN BLADDER APICAL MEMBRANE [J].
CHANG, A ;
HAMMOND, TG ;
SUN, TT ;
ZEIDEL, ML .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 1994, 267 (05) :C1483-C1492
[9]  
CHANG A, 1994, CELL PHYSL, V36, pC1483
[10]   A GUINEA-PIG MODEL FOR STUDY OF BLADDER MAST-CELL FUNCTION - HISTAMINE-RELEASE AND SMOOTH-MUSCLE CONTRACTION [J].
CHRISTENSEN, MM ;
KEITH, I ;
RHODES, PR ;
GRAZIANO, FM ;
MADSEN, PO ;
BRUSKEWITZ, RC ;
SABAN, R .
JOURNAL OF UROLOGY, 1990, 144 (05) :1293-1300