Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase‐2 induction by capsaicin and related analogs in macrophages

Chen, Ching-Wen; Lee, Sho Tone; Wu, Wen Tung; Fu, Wen‐Mei; Ho, Feng-Ming; Lin, Wan-Wan

doi:10.1038/sj.bjp.0705533

Cited by 118 publications

(104 citation statements)

References 47 publications

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“…The HCl-induced increase in PAF was abolished by the TRPV1 receptor antagonist IRTX. The increase in PAF levels in mucosa and supernatant, however, was not affected by neural block with TTX, indicating that production of PAF required no axonal conductance and most likely originated from the esophageal epithelium, consistent with the demonstrated presence of TRPV1 in nonneural cells such as keratinocytes of the epidermis (57,58), the human keratinocyte cell line HaCat (57), the human bronchial epithelial cell line BEAS-2B (65), bladder urothelium and smooth muscle (7,8), liver (51), polymorphonuclear granulocytes (30), and macrophages (17).…”

Section: Resultsmentioning

confidence: 60%

HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa

Cheng¹,

Monte²,

Ma³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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To test whether transient receptor potential channel vanilloid subfamily member-1 (TRPV1) mediates acid-induced inflammation in the esophagus, a tubular segment of esophageal mucosa was tied at both ends, forming a sac. The sac was filled with 0.01 N HCl (or Krebs buffer for control) and kept in oxygenated Krebs buffer at 37°C. The medium around the sac (supernatant) was collected after 3 h. Supernatant of the HCl-filled sac abolished contraction of esophageal circular muscle strips in response to electric field stimulation. Contraction was similarly abolished by supernatant of mucosal sac filled with the TRPV1 agonist capsaicin (10 Ϫ6 M). These effects were reversed by the selective TRPV1 antagonist 5Ј-iodoresiniferatoxin (IRTX) and by the plateletactivating factor (PAF) receptor antagonist CV9388. Substance P and CGRP levels in mucosa and in supernatant increased in response to HCl, and these increases were abolished by IRTX and by tetrodotoxin (TTX) but not affected by CV9388, indicating that substance P and CGRP are neurally released and PAF independent. In contrast, the increase in PAF was blocked by IRTX but not by TTX. Presence of TRPV1 receptor was confirmed by RT-PCR and by Western blot analysis in whole mucosa and in esophageal epithelial cells enzymatically isolated and sorted by flow cytometry or immunoprecipitated with cytokeratin antibodies. In epithelial cells PAF increased in response to HCl, and the increase was abolished by IRTX. We conclude that HCl-induced activation of TRPV1 receptors in esophageal mucosa causes release of substance P and CGRP from neurons and release of PAF from epithelial cells. smooth muscle; signal transduction; platelet-activating factor TRANSIENT RECEPTOR POTENTIAL channel vanilloid subfamily member-1 (TRPV1, also known as VR1) was originally described in primary sensory neurons as a receptor for capsaicin and related natural irritants (collectively referred to as vanilloids) (61). TRPV1 is a nonselective cation channel expressed by several cell types including sensory nerves. It is activated by heat, by the pungent ingredient of chili peppers, capsaicin, or by endogenous hydrogen ions released in tissues during inflammation (61) or present in gastric reflux. TRPV1 is now believed to function as a molecular integrator of noxious stimuli, including acids, heat, pollutants with negative electric charge, and endogenous proinflammatory substances (23). TRPV1 activation in primary afferent neurons evokes the sensation of burning pain and induces neurogenic inflammation by the release of substance P and calcitonin gene-related peptide (CGRP) (65, 66). Upregulated TRPV1 expression has been demonstrated in disease states such as inflammatory bowel disease (66) and irritable bowel syndrome (15) and, more recently, in esophageal submucosal neurons of esophagitis patients (5, 41).TRPV1-associated "neurogenic inflammation" has been examined in several systems, particularly in the airways, and to a lesser extent in the digestive tract. In the digestive tract most publications have ...

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Section: Resultsmentioning

confidence: 60%

HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa

Cheng¹,

Monte²,

Ma³

et al. 2009

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…Although the mechanism of TRPV1 channel activation after irradiation is still unknown, possible mediators include radiation-induced reactive oxygen species and secondary generation of nitric oxide in irradiated cells, 33) or radiation-induced extracellular release of ATP from cells, we have reported. [34][35][36][37] On the other hand, it is well known that TRPV1 channel is involved in inflammation and pain sensation, [38][39][40][41] and TRPV1 channel inhibitors are candidates as analgesic drugs to relieve cancer pain. 42,43) Therefore, TRPV1 inhibitors might offer dual benefits in cancer therapy, having both anti-inflammatory and radiosensitizing actions.…”

Section: Resultsmentioning

confidence: 99%

Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

Nishino

Tanamachi

Nakanishi

et al. 2016

Biological & Pharmaceutical Bulletin

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Radiosensitizers are used in cancer therapy to increase the γ-irradiation susceptibility of cancer cells, including radioresistant hypoxic cancer cells within solid tumors, so that radiotherapy can be applied at doses sufficiently low to minimize damage to adjacent normal tissues. Radiation-induced DNA damage is repaired by multiple repair systems, and therefore these systems are potential targets for radiosensitizers. We recently reported that the transient receptor potential vanilloid type 1 (TRPV1) channel is involved in early responses to DNA damage after γ-irradiation of human lung adenocarcinoma A549 cells. Therefore, we hypothesized that TRPV1 channel inhibitors would have a radiosensitizing effect by blocking repair of radiation-induced cell damage. Here, we show that pretreatment of A549 cells with the TRPV1 channel inhibitors capsazepine, AMG9810, SB366791 and BCTC suppressed the γ-ray-induced activation of early DNA damage responses, i.e., activation of the protein kinase ataxia-telangiectasia mutated (ATM) and accumulation of p53-binding protein 1 (53BP1). Further, the decrease of survival fraction at one week after γ-irradiation (2.0 Gy) was enhanced by pretreatment of cells with these inhibitors. On the other hand, inhibitor pretreatment did not affect cell viability, the number of apoptotic or necrotic cells, or DNA synthesis at 24 h after irradiation. These results suggest that inhibition of DNA repair by TRPV1 channel inhibitors in irradiated A549 cells caused gradual loss of proliferative ability, rather than acute facilitation of apoptosis or necrosis. TRPV1 channel inhibitors could be novel candidates for radiosensitizers to improve the efficacy of radiation therapy, either alone or in combination with other types of radiosensitizers. Key words γ-ray; radiosensitizer; transient receptor potential vanilloid type 1 channelRadiation therapy plays an important role in treatment of numerous cancers, 1) because ionizing radiation induces potentially lethal DNA damage, such as DNA double-strand breaks (DSBs). Although DSBs cause cell death or genomic instability, 2,3) they can be repaired by mechanisms such as non-homologous end joining (NHEJ) or homologous recombination (HR). NHEJ rejoins the DNA ends without requiring sequence homologies, and is mediated by a DNA-dependent protein kinase holoenzyme. On the other hand, HR processes use undamaged homologous DNA sequences (sister chromatid or the homologous chromosome) to ensure the fidelity of the repair process. [4][5][6] The DNA damage response pathways protect genomic integrity and act as a barrier against cancer, 7) and are important for recovery of irradiated normal cells. However, overexpression of DNA repair proteins is involved in radioresistance of cancer cells, [8][9][10] and therefore these mechanisms also decrease the efficiency of radiation therapy.Since ionizing radiation does not discriminate between cancer cells and normal cells, damage to normal tissues is usually a dose-limiting factor in radiation therapy. In addition, many solid ...

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“…However, a number of recent pharmacological, genetic, radioligand binding and immunohistochemical studies suggest widespread distribution and functionality of TRPV1 across the CNS (Cavanaugh et al, 2011;Goswami et al, 2010;Han et al, 2013;O'Sullivan et al,2000;Sanchez et al, 2001). TRPV1 is also found on nonneuronal cells such as keratinocytes (Southall et al, 2003), bladder urothelium (Lazzeri et al, 2004), smooth muscle (Birder et al, 2002), liver (Reilly et al, 2003), polymorphonuclear granulocytes (Heiner et al, 2003), pancreatic β-cells (Akiba et al, 2004), endothelial cells (Golech et al, 2004), lymphocytes (Saunders et al, 2007) and macrophages (Chen et al, 2003). (Cavanaugh et al, 2011;Cristino et al, 2006;Mezey et al, 2000;Roberts et al, 2004) Midbrain and hindbrain regions…”

Section: Localisationmentioning

confidence: 99%

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

Madasu

Okine

Olango

et al. 2016

Pharmacological Research

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Signal transduction for inhibition of inducible nitric oxide synthase and cyclooxygenase‐2 induction by capsaicin and related analogs in macrophages

Cited by 118 publications

References 47 publications

HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa

HCl-activated neural and epithelial vanilloid receptors (TRPV1) in cat esophageal mucosa

Radiosensitizing Effect of TRPV1 Channel Inhibitors in Cancer Cells

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

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