Repeated Cold Stress Reduces Cyclophosphamide-Induced Cystitis/Bladder Pain and Macrophage Activity in Mice

Tsubota, Maho; Miyamoto, Tomoyoshi; Hiruma, Shingo; Saeki, Haruka; Miyazaki, Takaya; Sekiguchi, Fumiko; Funakami, Yoshinori; Kawabata, Atsufumi

doi:10.1159/000461588

Cited by 2 publications

(2 citation statements)

References 16 publications

(27 reference statements)

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“…Before behavioural tests, mice were placed on a raised wire mesh under a clear plastic box (23.5 × 16.6 × 12.4 cm) and acclimated to the experimental environment for 1 hour. As described in detail elsewhere, bladder pain‐like nociceptive behaviour, such as licking/biting the external urethral opening or the surrounding skin area and pressing the lower abdomen against the floor, was counted for 30 minutes. In the evaluation of referred hyperalgesia, a mechanical stimulation was applied to the skin region between the anus and urethral opening of mice, using four distinct von Frey filaments with strengths of 0.008, 0.07, 0.4 and 1.0 g in an ascending order.…”

Section: Methodsmentioning

confidence: 99%

Involvement of NF‐κB in the upregulation of cystathionine‐γ‐lyase, a hydrogen sulfide‐forming enzyme, and bladder pain accompanying cystitis in mice

Ozaki

Tsubota

Sekiguchi

et al. 2017

Clin Exp Pharma Physio

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Hydrogen sulfide (H S) is generated from l-cysteine by multiple enzymes including cystathionine-γ-lyase (CSE), and promotes nociception by targeting multiple molecules such as Ca 3.2 T-type Ca channels. Bladder pain accompanying cyclophosphamide (CPA)-induced cystitis in mice has been shown to involve the functional upregulation of the CSE/H S/Ca 3.2 pathway. Therefore, we investigated whether NF-κB, as an upstream signal of the CSE/H S system, contributes to bladder pain in mice with CPA-induced cystitis. Bladder pain-like nociceptive behaviour was observed in CPA-treated mice, and referred hyperalgesia was evaluated by the von Frey test. Isolated bladder weights were assessed to estimate bladder swelling, and protein levels were measured by Western blotting. CPA, administered intraperitoneally, induced nociceptive behaviour, referred hyperalgesia and increased bladder weights in mice. β-Cyano-l-alanine, a reversible selective CSE inhibitor, prevented CPA-induced nociceptive behaviour, referred hyperalgesia, and, in part, increases in bladder weight. CPA markedly increased phosphorylated NF-κB p65 levels in the bladder, an effect that was prevented by pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor. PDTC and curcumin, which inhibits NF-κB signals, abolished CPA-induced nociceptive behaviour, referred hyperalgesia and, in part, increases in bladder weight. CPA caused the overexpression of CSE in the bladder, and this was prevented by PDTC or curcumin. The CPA-induced activation of NF-κB signals appeared to cause CSE overexpression in the bladder, contributing to bladder pain and in part swelling, possibly through H S/Ca 3.2 signaling. Therefore, NF-κB-inhibiting compounds including curcumin may be useful for the treatment of cystitis-related bladder pain.

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Section: Methodsmentioning

confidence: 99%

Involvement of NF‐κB in the upregulation of cystathionine‐γ‐lyase, a hydrogen sulfide‐forming enzyme, and bladder pain accompanying cystitis in mice

Ozaki

Tsubota

Sekiguchi

et al. 2017

Clin Exp Pharma Physio

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“…Diabetes increases the incidence and severity of IC/BPS ( 19 ). The recognition of the importance of local inflammation to the development of cystitis highlights the importance of studies of the major player for innate immunity, bladder macrophages ( 20 ). A recent study has demonstrated a 6-fold increase in bladder monocytes/macrophages in IC/BPS patients compared to healthy controls ( 21 ).…”

Section: Discussionmentioning

confidence: 99%

NLRP3+ macrophages aggravate inflammatory cystitis in diabetes

Peng

Gao

2022

Front. Immunol.

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Inflammatory macrophages play a pivotal role in the progression of inflammatory cystitis. Formation of NOD-, LRR- and PYD domains-containing protein 3 (NLRP3) inflammasome triggers the activation of caspase-1/IL-1β signaling cascades to mediate inflammatory response. However, it is not known whether NLRP3 activation in macrophages during cystitis may differ in normal or diabetic setting as well as the importance of it. In this study, we found that NLRP3 levels significantly increased in bladder macrophages in diabetic mice that underwent cystitis. Moreover, bladder macrophages from diabetic mice appeared to have increased their potential of growth, migration and phagocytosis. Furthermore, specific depletion of NLRP3 in macrophages alleviated the severity of cystitis in diabetic mice, but not in non-diabetic mice. Together, our data suggest that NLRP3 depletion in macrophages may be a promising strategy for treating diabetic cystitis.

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Repeated Cold Stress Reduces Cyclophosphamide-Induced Cystitis/Bladder Pain and Macrophage Activity in Mice

Cited by 2 publications

References 16 publications

Involvement of NF‐κB in the upregulation of cystathionine‐γ‐lyase, a hydrogen sulfide‐forming enzyme, and bladder pain accompanying cystitis in mice

Involvement of NF‐κB in the upregulation of cystathionine‐γ‐lyase, a hydrogen sulfide‐forming enzyme, and bladder pain accompanying cystitis in mice

NLRP3+ macrophages aggravate inflammatory cystitis in diabetes

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