Tumor Necrosis Factor Promotes Differential Trafficking of Bladder Mast Cells in Neurogenic Cystitis

Chen, Michael C.; Blunt, Lynn W.; Pins, Michael; Klumpp, David J.

doi:10.1016/s0022-5347(05)00171-0

Cited by 30 publications

(31 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Although many areas appeared histologically normal in bladders of mice infected with PRV, focal areas exhibited dilated blood vessels, leukocytic infiltrate, and signs of edema at PID5 (compare Fig. 4, A and B), consistent with previous characterization of bladder inflammation in the murine neurogenic cystitis model (8). In contrast, colon tissue from PRV-infected mice was indistinguishable from normal tissue and showed no evidence of edema, vascular changes, leukocytic infiltrate, or damage to the epithelium or lamina propria or smooth muscle (compare Fig.…”

Section: Resultssupporting

confidence: 89%

“…Vascular permeability associated with pelvic inflammation has been previously characterized by examining extravasation of Evans blue dye from the circulation into tissues (8,18,41). We quantified Evans blue dye extravasation in the bladder and colon of PRV-infected mice at PID5.…”

Section: Resultsmentioning

confidence: 99%

“…Neurogenic cystitis was induced by injection of 2.29 ϫ 10 6 plaque-forming units of Bartha's PRV in the abductor caudalis dorsalis (ACD) muscle with a 26-gauge Hamilton syringe while maintaining the animals under isoflurane anesthesia. Ultravioletirradiated/heat-inactivated PRV stocks were employed as negative control inocula in sham-treated mice as previously described (8). Both sham and PRV-infected mice were hydrated daily by subcutaneous injection of 3 ml of saline in the shoulder region, because previous experiments indicated that PRV altered fluid intake (Chen MC and Klumpp DJ, unpublished observations).…”

Section: Animalsmentioning

confidence: 99%

See 2 more Smart Citations

Organ cross talk modulates pelvic pain

Rudick

Chen

Mongiu

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

100

111

View full text Add to dashboard Cite

(IC) is a chronic bladder inflammatory disease of unknown etiology that is often regarded as a neurogenic cystitis. IC is associated with urothelial lesions, voiding dysfunction, and pain in the pelvic/perineal area, and diet can exacerbate IC symptoms. In this study, we used a murine neurogenic cystitis model to investigate the development of pelvic pain behavior. Neurogenic cystitis was induced by the injection of Bartha's strain of pseudorabies virus (PRV) into the abductor caudalis dorsalis tail base muscle of female C57BL/6J mice. Infectious PRV virions were isolated only from the spinal cord, confirming the centrally mediated nature of this neurogenic cystitis model. Pelvic pain was assessed using von Frey filament stimulation to the pelvic region, and mice infected with PRV developed progressive pelvic pain. Pelvic pain was alleviated by 2% lidocaine instillation into either the bladder or the colon but not following lidocaine instillation into the uterus. The bladders of PRV-infected mice showed markers of inflammation and increased vascular permeability compared with controls. In contrast, colon histology was normal and vascular permeability was unchanged, suggesting that development of pelvic pain was due only to bladder inflammation. Bladder-induced pelvic pain was also exacerbated by colonic administration of a subthreshold dose of capsaicin. These data indicate organ cross talk in pelvic pain and modulation of pain responses by visceral inputs distinct from the inflamed site. Furthermore, these data suggest a mechanism by which dietary modification benefits pelvic pain symptoms.bladder; interstitial cystitis; diet INTERSTITIAL CYSTITIS (IC), also known as painful bladder syndrome, is a chronic bladder inflammatory disease with unknown etiology that afflicts as many as 1 million patients in the United States, with females comprising ϳ90% of patients (21). Symptoms of IC include pelvic and/or perineal pain, urinary frequency, urgency, and nocturia (17,20,32,39). IC is often regarded as a neurogenic cystitis due to voiding dysfunction and the partial efficacy of sacral nerve stimulation or neuropharmacological therapies in some patients that suggests a neuronal component. Supporting this idea, cats are susceptible to feline IC, a disease that closely mimics human IC and is associated with increased activity in the sympathetic nervous system (40). Since IC symptoms can flare in response to certain foods (e.g., tomatoes), dietary modification is commonly employed by IC patients, although evidence of altered urine properties as the mechanism for dietary effects is lacking.One model of IC pathogenesis involves a positive feedback loop, whereby substance P-containing peripheral nerves stimulate mast cells, in turn releasing inflammatory mediators that induce urothelial inflammation (15). Furthermore, histamine release by mast cells feeds back onto peripheral nerves to cause sustained release of substance P and mast cell activation. Consistent with this model, patients with IC show elevated mast cell counts ...

show abstract

Section: Resultssupporting

confidence: 89%

Section: Resultsmentioning

confidence: 99%

Section: Animalsmentioning

confidence: 99%

See 1 more Smart Citation

Organ cross talk modulates pelvic pain

Rudick

Chen

Mongiu

et al. 2007

American Journal of Physiology-Regulatory, Integrative and Comp

Self Cite

100

111

View full text Add to dashboard Cite

show abstract

“…We reported that PRV induced a neurogenic cystitis in mice that increased vascular permeability, induced leukocyte influx, and resulted in differential trafficking of mast cell pools within the bladder (10). Furthermore, these events did not occur in TNF receptor-deficient mice, suggesting that TNF is essential for mast cell trafficking in neurogenic cystitis.…”

mentioning

confidence: 95%

Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis

Chen

Mudge²,

Klumpp³

2006

American Journal of Physiology-Renal Physiology

Self Cite

View full text Add to dashboard Cite

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.

show abstract

“…Evidence from both rodent and humans suggest that mast cells play an important role in these conditions. It has been shown that activated mast cells are associated with rodent neurogenic cystitis induced by the Bartha strain of pseudorabies virus (PRV) (Chen et al, 2006;Jasmin et al, 2000). Moreover, clinical studies have demonstrated an elevated number of mast cells in the lamina propria of IC bladder biopsies (Leiby et al, 2007) and increased urinary histamine metabolites (el-Mansoury et al, 1994).…”

mentioning

confidence: 99%

The role of histamine in neurogenic inflammation

Rosa

Fantozzi

2013

British J Pharmacology

163

138

View full text Add to dashboard Cite

The term 'neurogenic inflammation' has been adopted to describe the local release of inflammatory mediators, such as substance P and calcitonin gene-related peptide, from neurons. Once released, these neuropeptides induce the release of histamine from adjacent mast cells. In turn, histamine evokes the release of substance P and calcitonin gene-related peptide; thus, a bidirectional link between histamine and neuropeptides in neurogenic inflammation is established. The aim of this review is to summarize the most recent findings on the role of histamine in neurogenic inflammation, with particular regard to nociceptive pain, as well as neurogenic inflammation in the skin, airways and bladder. LINKED ARTICLESThis article is part of a themed issue on Histamine Pharmacology Update. To view the other articles in this issue visit http://dx.doi.org/10.1111/bph.2013.170.issue-1 Abbreviations CGRP, calcitonin gene-related peptide; ERs, oestrogen receptors; GERD, gastro-oesophageal reflux disease; HDC, histidine decarboxylase; IC, interstitial cystitis; PBS, painful bladder syndrome; SP, substance P; VIP, vasoactive intestinal peptide IntroductionThe term 'neurogenic inflammation' describes the local release of inflammatory mediators, such as substance P (SP) and calcitonin gene-related peptide (CGRP), from afferent neurons. The initial evidence for neurogenic vasodilatation in response to noxious stimuli was obtained in the skin of humans and other mammals (Schmelz and Petersen, 2001), but now it is recognized that neurogenic inflammation also occurs in visceral organs. The inflammatory response evoked by the activation of the sensory nerve fibres, which includes local vasodilatation, plasma extravasation, leukocyte and platelet adhesion, and mast cell degranulation, is brought about by neuropeptides released from the peripheral endings of sensory neurons upon stimulation of the primary sensory terminals. Both SP in neurons and histamine in mast cells have a dual mediator role in neurogenic inflammation (Figure 1). In fact, as demonstrated by Foreman and Jordan (1984), injury causes activation of sensory nerve endings either directly or through the release of histamine from the adjacent mast cells. The action potential generated travels orthodromically to the dorsal horn of the spinal cord and spreads to other branches of the same neurons, which will then release SP from their terminals or varicosities. The released SP, as well as contributing itself to local vasodilatation, induces histamine release from the adjacent mast cells, which produces flare and further activates other sensory nerve endings (Foreman et al., 1983).Neutrophils, whose responsiveness to SP has been repeatedly demonstrated, contribute to the inflammatory soup following neurogenic inflammation. In fact, neutrophils express the SP receptors NK 1, NK2 and NK3, and when stimulated with SP induce the expression of COX-2 and PGE2 release in the nanomolar range (Gallicchio et al., 2008;. Furthermore, SP at micromolar concentrations primes neutrophils, thus en...

show abstract

Tumor Necrosis Factor Promotes Differential Trafficking of Bladder Mast Cells in Neurogenic Cystitis

Abstract: These data indicate that neurogenic cystitis is associated with the differential trafficking and activation of distinct mast cell pools in the bladder. Since TNF mediates these events, anti-TNF therapy may mitigate the pathogenesis of neurogenic cystitis.

Cited by 30 publications

References 15 publications

Organ cross talk modulates pelvic pain

Organ cross talk modulates pelvic pain

Urothelial lesion formation is mediated by TNFR1 during neurogenic cystitis

The role of histamine in neurogenic inflammation

Contact Info

Product

Resources

About