Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P15088 (mast cell)
 14,925 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mast cell numbers are significantly increased in bladder disorders including malignancy and interstitial cystitis, but their precise role has been difficult to determine. We characterized the role of mast cells on gene regulation associated with antigen-induced bladder inflammation in mice. For this purpose, we examined the responses in mast cell-deficient (Kit(W)/Kit(W-v)), congenic normal (+/+), and Kit(W)/Kit(W-v) mice that were reconstituted with bone marrow stem cells (BMR) to restore mast cells. All mice were actively sensitized and challenged intravesically with either saline or specific antigen. Bladder inflammation occurred in +/+ and BMR but not the Kit(W)/Kit(W-v) mice. Gene expression was determined using mouse cDNA expression arrays. Self-organizing maps, performed without preconditions, indicated gene expression changes dependent on the presence of mast cells. These genes were upregulated in bladders isolated from antigen challenge of +/+, not altered in Kit(W)/Kit(W-v), and were upregulated in BMR mice. Taken together these results demonstrate an important role for mast cells in allergic cystitis and indicate that mast cells can alter their environment by regulating tissue gene expression.
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PMID:Mast cell regulation of inflammation and gene expression during antigen-induced bladder inflammation in mice. 1159 90

Interstitial cystitis is a disease characterized by pain occurring as the urinary bladder is gradually filling up. Its pathophysiology is unknown. The cause could be either a membrane permeability disorder, a mast cell disturbance in the bladder wall, or an autoimmune process involving the bladder. The diagnosis is essentially clinical but endoscopies and biopsies are required to rule out vesical cancers. Treatments is difficult and based on a combination of sanitary and dietary regimens, as well as drugs administered orally or infused within the bladder. Surgical treatment must remain exceptional.
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PMID:[Interstitial cystitis]. 1185 61

Inflammatory bladder disorders such as interstitial cystitis (IC) deserve attention since a major problem of the disease is diagnosis. IC affects millions of women and is characterized by severe pain, increased frequency of micturition, and chronic inflammation. Characterizing the molecular fingerprint (gene profile) of IC will help elucidate the mechanisms involved and suggest further approaches for therapeutic intervention. Therefore, in the present study we used established animal models of cystitis to determine the time course of bladder inflammatory responses to antigen, Escherichia coli lipopolysaccharide (LPS), and substance P (SP) by morphological analysis and cDNA microarrays. The specific aim of the present study was to compare bladder inflammatory responses to antigen, LPS, and SP by morphological analysis and cDNA microarray profiling to determine whether bladder responses to inflammation elicit a specific universal gene expression response regardless of the stimulating agent. During acute bladder inflammation, there was a predominant infiltrate of polymorphonuclear neutrophils into the bladder. Time-course studies identified early, intermediate, and late genes that were commonly up-regulated by all three stimuli. These genes included: phosphodiesterase 1C, cAMP-dependent protein kinase, iNOS, beta-NGF, proenkephalin B and orphanin, corticotrophin-releasing factor (CRF) R, estrogen R, PAI2, and protease inhibitor 17, NFkB p105, c-fos, fos-B, basic transcription factors, and cytoskeleton and motility proteins. Another cluster indicated genes that were commonly down-regulated by all three stimuli and included HSF2, NF-kappa B p65, ICE, IGF-II and FGF-7, MMP2, MMP14, and presenilin 2. Furthermore, we determined gene profiles that identify the transition between acute and chronic inflammation. During chronic inflammation, the urinary bladder presented a predominance of monocyte/macrophage infiltrate and a concomitant increase in the expression of the following genes: 5-HT 1c, 5-HTR7, beta 2 adrenergic receptor, c-Fgr, collagen 10 alpha 1, mast cell factor, melanocyte-specific gene 2, neural cell adhesion molecule 2, potassium inwardly-rectifying channel, prostaglandin F receptor, and RXR-beta cis-11-retinoic acid receptor. We conclude that microarray analysis of genes expressed in the bladder during experimental inflammation may be predictive of outcome. Further characterization of the inflammation-induced gene expression profiles obtained here may identify novel biomarkers and shed light into the etiology of cystitis.
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PMID:Gene expression profiling of mouse bladder inflammatory responses to LPS, substance P, and antigen-stimulation. 1205 14

In this workshop the participants were asked to consider the role of pathology in the diagnosis and management of interstitial cystitis (IC). Currently, the NIDDK definition of IC is made on clinical criteria; bladder biopsy is not required for the clinical work-up and histology is not used as a diagnostic criterion. The literature review described the most common pathological findings to be epithelial denudation or ulceration, mononuclear inflammation, edema, congestion, hemorrhage, and mast cell activation. These pathological changes were not universal or specific with 55% of IC subjects in one study having histology that was normal and indistinguishable from control subjects. Presentations were made which generally confirmed an association between abnormal pathology and more severe disease as determined by symptoms, cystoscopic capacity, and prognosis. During the workshop it was clear that whether or not a biopsy was performed depended on a number of factors, for example, country of origin, the research interest of the unit, and the desire to exclude malignancy on histological grounds. The consensus, which was not unanimous, was that bladder biopsy was a-non-mandatory test in the clinical work-up of the patient with IC but that urine cytology should be performed. It was discussed that bladder biopsy be an optional test and particularly relevant when one was suspicious of other conditions and in IC research. It was hoped that bladder biopsy pathology will give clues to contributory pathogenic processes such as epithelial dysfunction and inflammation; and in the future, with the help of molecular biology, may help determine etiology.
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PMID:Pathology of interstitial cystitis. 1464 7

Recent advances in basic and clinical research indicate that interstitial cystitis (IC) is a form of neurogenic inflammation, thereby opening new avenues for research into this painful disease. With this in mind, we have recently developed a rat model of neurogenic inflammation of the bladder produced by a central nervous system viral disease. As in IC, the inflammation in this model develops without direct injury or trauma to the bladder, is non-infectious, and is limited to the bladder. Our most recent studies aimed at further testing the similarity of this animal model to IC by assessing the urine content in histamine with the occurrence of mast cell degranulation in the bladder wall. We further verified for a sex difference in the occurrence of the disease. Our results showed increased levels of urine histamine and mast cell activation during the early stages of the disease. We additionally observed that females had a greater degree of plasma extravasation, while males had a greater cellular infiltration together with worse behavioral signs. Gonadectomy prevented the bladder inflammation altogether in both males and females. These findings further validate our model of neurogenic cystitis to study the neurogenic component of IC.
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PMID:Experimental neurogenic cystitis. 1508 15

Interstitial cystitis (IC) is a debilitating chronic inflammatory disorder of the bladder. It affects predominantly middle-aged Caucasian women. The diagnosis, made from the combination of symptoms, cystoscopic findings and bladder biopsies, is often delayed in the gynaecology setting because of a low index of suspicion. The pathophysiology is incompletely understood, although mast cell activation, altered bladder epithelial permeability and sensory afferent nerve up-regulation are thought to play key roles. Recent theories include the role of an antiproliferative factor. A wide assortment of therapies is available and many more are under trial. Until the causes and pathogenesis of IC are unraveled, mainstream medical treatment will remain palliative and cystectomy with urinary diversion, the only potential cure. In addition to our long experience on managing this disorder, we present a comprehensive review of the current thoughts on the aetiology and management of IC.
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PMID:Interstitial cystitis. 1520 11

Increased mast cell numbers and mast cell activation represent one of the prevalent etiologic theories for interstitial cystitis, an inflammatory condition in the bladder. This study was designed primarily to determine whether increased mast cell tryptase in the bladder wall may play a role in activating bladder endothelial cell phospholipase A(2) (PLA(2)), leading to increased inflammatory phospholipid metabolite accumulation, which may propagate the inflammatory process. We stimulated human bladder microvascular endothelial cells with thrombin or tryptase and measured the activation of PLA(2) and the production of multiple membrane phospholipid-derived inflammatory mediators. Thrombin and tryptase stimulation resulted in activation of a Ca(2+)-independent PLA(2), leading to increased release of arachidonic acid and prostacyclin and increased production of platelet-activating factor. These responses were blocked completely by pretreatment of human bladder microvascular endothelial cells with the Ca(2+)-independent PLA(2)-selective inhibitor bromoenol lactone. The combination of increased prostacyclin and platelet-activating factor in the bladder circulation may result in vasodilation and increased polymorphonuclear leukocyte adherence to the endothelium and may facilitate recruitment of polymorphonuclear leukocytes to the bladder wall of patients with interstitial cystitis.
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PMID:Protease-activated receptor stimulation activates a Ca2+-independent phospholipase A2 in bladder microvascular endothelial cells. 1556 75

Fibromyalgia (FMS) is a debilitating disorder characterized by chronic diffuse muscle pain, fatigue, sleep disturbance, depression and skin sensitivity. There are no genetic or biochemical markers and patients often present with other comorbid diseases, such as migraines, interstitial cystitis and irritable bowel syndrome. Diagnosis includes the presence of 11/18 trigger points, but many patients with early symptoms might not fit this definition. Pathogenesis is still unknown, but there has been evidence of increased corticotropin-releasing hormone (CRH) and substance P (SP) in the CSF of FMS patients, as well as increased SP, IL-6 and IL-8 in their serum. Increased numbers of activated mast cells were also noted in skin biopsies. The hypothesis is put forward that FMS is a neuro-immunoendocrine disorder where increased release of CRH and SP from neurons in specific muscle sites triggers local mast cells to release proinflammatory and neurosensitizing molecules. There is no curative treatment although low doses of tricyclic antidepressants and the serotonin-3 receptor antagonist tropisetron, are helpful. Recent nutraceutical formulations containing the natural anti-inflammatory and mast cell inhibitory flavonoid quercetin hold promise since they can be used together with other treatment modalities.
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PMID:Fibromyalgia--new concepts of pathogenesis and treatment. 1656 42

Interstitial cystitis (IC) is a chronic bladder inflammatory disease of unknown etiology that shares similarities with Crohn's disease and psoriasis. IC, often regarded as a neurogenic cystitis, is associated with urothelial lesions that likely compromise the bladder permeability barrier and thereby contribute to patient morbidity. Here, we use a murine model of neurogenic cystitis to investigate the mechanism of urothelial lesion formation and find that urothelial apoptosis induces formation of lesions. Lesions formed in wild-type mice but not in mice deficient in TNF, TNF receptors, or mast cells. In urothelial cultures, only siRNAs targeting TNFR1, but not TNFR2, blocked TNF-induced apoptosis, indicating a primary role for TNFR1. Trans-epithelial resistance, a measure of bladder barrier function, decreased during neurogenic cystitis in wild-type and TNFR2(-/-) mice but was stabilized in TNF(-/-) mice. Anti-TNF antibodies both altered bladder mast cell localization and stabilized barrier function. Based on these findings, we conclude that mast cell activation and release of TNF drive urothelial apoptosis and lesion formation in a murine neurogenic cystitis model, and we hypothesize that anti-TNF therapy may stabilize bladder barrier function in IC patients.
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PMID:Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis. 1662 79

Interstitial cystitis (IC) is a chronic disorder diagnosed by symptomatology of pelvic pain and urinary frequency, which are extremely variable and unpredictable fluctuating among patients. IC has recently been found combined with some allergic disorders and histopathologic abnormalities resembling that of allergic disorders, including mast cell activation, histamine release and eosinophil infiltration. Therefore, it could be cautiously postulated that IC is one of the allergic disorders of the urogenital system. A 28-year-old Caucasian female patient, who was diagnosed with asthma and allergic rhinitis, suffered from bladder symptoms of frequency, urgency and pelvic pain for the past 3 years. The symptoms disturbed her every day and were intractable for treatment. Urologists concluded that she had interstitial cystitis. Specific immunotherapy (SIT) was recommended for her allergic symptoms. While taking specific immunotherapy, she had anaphylaxis. She still had the reaction even with the 1000-fold diluted shot of SIT. Omalizumab was used for her allergic symptoms and possible prevention of anaphylactic reaction to SIT. Interestingly, she reported that her urogenital symptoms had subsided since omalizumab had been started. According to the published literature, we postulate that interstitial cystitis might be one of the IgE mediated, mast cell driven allergic disorders of the urogenital system. Therefore, in this case, the patient's bladder symptoms are successfully controlled primarily by anti-IgE therapy and the improvement could be maintained by SIT. We report, for the first time, a case of interstitial cystitis with allergic rhinitis and asthma, successfully treated by anti-IgE therapy and specific immunotherapy.
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PMID:Is interstitial cystitis an allergic disorder?: A case of interstitial cystitis treated successfully with anti-IgE. 1677 42


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