scholarly journals Negative Cellular Effects of Urban Particulate Matter on Human Keratinocytes Are Mediated by P38 MAPK and NF-κB-dependent Expression of TRPV 1

2018 ◽  
Vol 19 (9) ◽  
pp. 2660 ◽  
Author(s):  
Kitae Kwon ◽  
See-Hyoung Park ◽  
Byung Han ◽  
Sae Oh ◽  
Seung Lee ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Receptor Potential ◽  
Human Keratinocytes ◽  
Underlying Mechanism ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Reporter ◽  
Transient Receptor Potential Vanilloid ◽  
Urban Particulate Matter

Urban particulate matter (UPM) exerts negative effects on various human organs. Transient receptor potential vanilloid 1 (TRPV1) is a polymodal sensory transducer that can be activated by multiple noxious stimuli. This study aimed to explore the effects of the UPM 1648a on the expression of TRPV1, and its regulatory mechanisms in HaCaT cells. UPM enhanced TRPV 1 promoter-luciferase reporter activity. UPM also increased expression of the TRPV 1 gene as evidenced by increased mRNA and protein levels of TRPV 1. In addition, elucidation of the underlying mechanism behind the UPM-mediated effects on TRPV 1 expression revealed that UPM can upregulate expression of the TRPV1 gene by activating activator protein-1 (AP-1) and nuclear factor kappa B (NF-κB). The UPM treatment also altered Ca2+ influx and cell proliferation, as well as production of interleukin-8 (IL-8), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). In addition, these UPM-induced effects were attenuated by SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC). However, SP600125 and PD98059 did not alter the UPM-induced effects. Taken together, these findings indicate that UPM upregulates expression of the TRPV 1 gene, which is mediated by the p38 mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways and suggest that UPM is a potential irritant that can induce skin processes such as aging and inflammatory responses.

scholarly journals Supercooling Agent Icilin Blocks a Warmth-Sensing Ion Channel TRPV3

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Muhammad Azhar Sherkheli ◽  
Guenter Gisselmann ◽  
Hanns Hatt
Keyword(s):  
Ion Channel ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Human Keratinocytes ◽  
Transient Receptor Potential Vanilloid ◽  
Neural Cells ◽  
Hek 293 ◽  
Low Concentrations ◽  
293 Cells ◽  
Transient Receptor

Transient receptor potential vanilloid subtype 3 (TRPV3) is a thermosensitive ion channel expressed in a variety of neural cells and in keratinocytes. It is activated by warmth (33–39°C), and its responsiveness is dramatically increased at nociceptive temperatures greater than 40°C. Monoterpenoids and 2-APB are chemical activators of TRPV3 channels. We found that Icilin, a known cooling substance and putative ligand of TRPM8, reversibly inhibits TRPV3 activity at nanomolar concentrations in expression systems likeXenopus laevesoocytes, HEK-293 cells, and in cultured human keratinocytes. Our data show that icilin's antagonistic effects for the warm-sensitive TRPV3 ion channel occurs at very low concentrations. Therefore, the cooling effect evoked by icilin may at least in part be due to TRPV3 inhibition in addition to TRPM8 potentiation. Blockade of TRPV3 activity by icilin at such low concentrations might have important implications for overall cooling sensations detected by keratinocytes and free nerve endings in skin. We hypothesize that blockage of TRPV3 might be a signal for cool-sensing systems (like TRPM8) to beat up the basal activity resulting in increased cold perception when warmth sensors (like TRPV3) are shut off.

scholarly journals Investigating the Multitarget Mechanism of Traditional Chinese Medicine Prescription for Cancer-Related Pain by Using Network Pharmacology and Molecular Docking Approach

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Jinyuan Chang ◽  
Lixing Liu ◽  
Yaohan Wang ◽  
Yutong Sui ◽  
Hao Li ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Transient Receptor Potential ◽  
Trp Channels ◽  
Receptor Potential ◽  
Binding Activity ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Transient Receptor Potential Vanilloid ◽  
Mitogen Activated Protein ◽  
Transient Receptor

Gu-tong formula (GTF) has achieved good curative effects in the treatment of cancer-related pain. However, its potential mechanisms have not been explored. We used network pharmacology and molecular docking to investigate the molecular mechanism and the effective compounds of the prescription. Through the analysis and research in this paper, we obtained 74 effective compounds and 125 drug-disease intersection targets to construct a network, indicating that quercetin, kaempferol, and β-sitosterol were possibly the most important compounds in GTF. The key targets of GTF for cancer-related pain were Jun proto-oncogene (JUN), mitogen-activated protein kinase 1 (MAPK1), and RELA proto-oncogene (RELA). 2204 GO entries and 148 pathways were obtained by GO and KEGG enrichment, respectively, which proved that chemokine, MAPK, and transient receptor potential (TRP) channels can be regulated by GTF. The results of molecular docking showed that stigmasterol had strong binding activity with arginine vasopressin receptor 2 (AVPR2) and C-X3-C motif chemokine ligand 1 (CX3CL1) and cholesterol was more stable with p38 MAPK, prostaglandin-endoperoxide synthase 2 (PTGS2), and transient receptor potential vanilloid-1 (TRPV1). In conclusion, the therapeutic effect of GTF on cancer-related pain is based on the comprehensive pharmacological effect of multicomponent, multitarget, and multichannel pathways. This study provides a theoretical basis for further experimental research in the future.

scholarly journals Activation of TRPV1 Prevents OxLDL-Induced Lipid Accumulation and TNF-α-Induced Inflammation in Macrophages: Role of Liver X Receptorα

2013 ◽  
Vol 2013 ◽  
pp. 1-14 ◽  
Author(s):  
Jin-Feng Zhao ◽  
Li-Chieh Ching ◽  
Yu Ru Kou ◽  
Shing-Jong Lin ◽  
Jeng Wei ◽  
...  
Keyword(s):  
Abc Transporters ◽  
Lipid Accumulation ◽  
Transient Receptor Potential ◽  
Density Lipoprotein ◽  
Receptor Potential ◽  
Underlying Mechanism ◽  
Transient Receptor Potential Vanilloid ◽  
Regulation Of Transcription ◽  
Mouse Bone Marrow ◽  
Trpv1 Antagonist

The transient receptor potential vanilloid type 1 (TRPV1) is crucial in the pathogenesis of atherosclerosis; yet its role and underlying mechanism in the formation of macrophage foam cells remain unclear. Here, we show increased TRPV1 expression in the area of foamy macrophages in atherosclerotic aortas of apolipoprotein E-deficient mice. Exposure of mouse bone-marrow-derived macrophages to oxidized low-density lipoprotein (oxLDL) upregulated the expression of TRPV1. In addition, oxLDL activated TRPV1 and elicited calcium (Ca2+) influx, which were abrogated by the pharmacological TRPV1 antagonist capsazepine. Furthermore, oxLDL-induced lipid accumulation in macrophages was ameliorated by TRPV1 agonists but exacerbated by TRPV1 antagonist. Treatment with TRPV1 agonists did not affect the internalization of oxLDL but promoted cholesterol efflux by upregulating the efflux ATP-binding cassette (ABC) transporters ABCA1 and ABCG1. Moreover, the upregulation of ABC transporters was mainly through liver X receptorα- (LXRα-) dependent regulation of transcription. Moreover, the TNF-α-induced inflammatory response was alleviated by TRPV1 agonists but aggravated by the TRPV1 antagonist and LXRαsiRNA in macrophages. Our data suggest that LXRαplays a pivotal role in TRPV1-activation-conferred protection against oxLDL-induced lipid accumulation and TNF-α-induced inflammation in macrophages.

scholarly journals Riboflavin Inhibits Histamine-Dependent Itch by Modulating Transient Receptor Potential Vanilloid 1 (TRPV1)

2021 ◽  
Vol 14 ◽  
Author(s):  
Kihwan Lee ◽  
Young In Choi ◽  
Sang-Taek Im ◽  
Sung-Min Hwang ◽  
Han-Kyu Lee ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Underlying Mechanism ◽  
Skin Lesions ◽  
Hek293 Cells ◽  
Flavin Mononucleotide ◽  
Transient Receptor Potential Vanilloid ◽  
Therapeutic Effects ◽  
Induced Currents ◽  
Transient Receptor

Riboflavin, also known as vitamin B2, isfound in foods and is used as a dietary supplement. Its deficiency (also called ariboflavinosis) results in some skin lesions and inflammations, such as stomatitis, cheilosis, oily scaly skin rashes, and itchy, watery eyes. Various therapeutic effects of riboflavin, such as anticancer, antioxidant, anti-inflammatory, and anti-nociceptive effects, are well known. Although some studies have identified the clinical effect of riboflavin on skin problems, including itch and inflammation, its underlying mechanism of action remains unknown. In this study, we investigated the molecular mechanism of the effects of riboflavin on histamine-dependent itch based on behavioral tests and electrophysiological experiments. Riboflavin significantly reduced histamine-induced scratching behaviors in mice and histamine-induced discharges in single-nerve fiber recordings, while it did not alter motor function in the rotarod test. In cultured dorsal root ganglion (DRG) neurons, riboflavin showed a dose-dependent inhibitory effect on the histamine- and capsaicin-induced inward current. Further tests wereconducted to determine whether two endogenous metabolites of riboflavin, flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD), have similar effects to those of riboflavin. Here, FMN, but not FAD, significantly inhibited capsaicin-induced currents and itching responses caused by histamine. In addition, in transient receptor potential vanilloid 1 (TRPV1)-transfected HEK293 cells, both riboflavin and FMN blocked capsaicin-induced currents, whereas FAD did not. These results revealed that riboflavin inhibits histamine-dependent itch by modulating TRPV1 activity. This study will be helpful in understanding how riboflavin exerts antipruritic effects and suggests that it might be a useful drug for the treatment of histamine-dependent itch.

scholarly journals Activation of transient receptor potential vanilloid 4 protects articular cartilage against IL-1β-induced inflammatory responses by regulating the CaMKK/AMPK/NF-κB signaling pathway

2021 ◽  
Author(s):  
Kyosuke Hattori ◽  
Nobunori Takahashi ◽  
Kenya Terabe ◽  
Yoshifumi Ohashi ◽  
Kenji Kishimoto ◽  
...  
Keyword(s):  
Articular Cartilage ◽  
Protein Kinase ◽  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Receptor Potential ◽  
Cartilage Tissue ◽  
Transient Receptor Potential Vanilloid ◽  
Compound C ◽  
Transient Receptor ◽  
Safranin O

Abstract Transient receptor potential vanilloid 4 (TRPV4) plays an important role in chondrocytes via Ca2+ signaling. However, its role in the progression of osteoarthritis is unclear. This study aimed to evaluate the effects of TRPV4 activation on articular cartilage and chondrocytes stimulated with interleukin (IL)-1β. Bovine and human articular chondrocytes were stimulated with various agents, including IL-1β, GSK1016790A (GSK101; a TRPV4 agonist), Compound C (an AMP-activated protein kinase (AMPK) inhibitor), and STO-609 (a calmodulin-dependent protein kinase kinase (CaMKK) inhibitor), and were processed for Western blot analysis and real-time PCR. The dimethylmethylene blue (DMMB) assay and Safranin O staining were also performed. GSK101 reversed the IL-1β-induced increase in expression of matrix metalloproteinase (MMP)-13 and decrease in expression of aggrecan. GSK101 also decreased proteoglycan release in the DMMB assay and retained Safranin O staining of articular cartilage tissue. Furthermore, GSK101 increased AMPK phosphorylation and decreased IL-1β-induced nuclear factor kappa B (NF-κB) phosphorylation. Compound C and STO-609 reversed the suppressive effects of GSK101 on NF-κB activation and MMP-13 expression. In conclusion, TRPV4 activation had chondroprotective effects on articular cartilage stimulated with IL-1β by activating CaMKK/AMPK and suppressing the NF-κB pathway. TRPV activators may offer a promising therapeutic option for preventing the progression of osteoarthritis.

scholarly journals TRPV1 Ablation Aggravates Inflammatory Responses and Organ Damage during Endotoxic Shock

2013 ◽  
Vol 20 (7) ◽  
pp. 1008-1015 ◽  
Author(s):  
Youping Wang ◽  
Donna H. Wang
Keyword(s):  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Endotoxic Shock ◽  
Elevated Serum ◽  
Receptor Potential ◽  
Organ Damage ◽  
Transient Receptor Potential Vanilloid ◽  
Hepatocellular Injury ◽  
Necrosis Factor Alpha ◽  
Trpv1 Channels

ABSTRACTTo test the hypothesis that ablation of transient receptor potential vanilloid type 1 (TRPV1) channels leads to exacerbated inflammatory responses and organ damage during endotoxic shock, lipopolysaccharide (LPS; 5 million endotoxin units/kg of body weight) was injected intraperitoneally (i.p.) into wild-type (WT) and TRPV1-null mutant (TRPV1−/−) mice. Mean arterial pressure and heart rate, determined by radiotelemetry, were severely depressed after LPS injection into WT and TRPV1−/−mice, with no distinction between the two strains. At 24 h after LPS injection, renal glomerular hypercellularity and hepatocellular injury were observed in both strains, accompanying further elevated serum levels of creatinine and alanine aminotransferase in TRPV1−/−mice compared to those in WT mice. At 6 or 24 h after LPS injection, neutrophil recruitment into kidneys and livers, serum cytokine (tumor necrosis factor alpha [TNF-α], interleukin 1β [IL-1β], IL-6) and renal chemokine (KC, macrophage inflammatory protein 2 [MIP-2]) levels, and renal VCAM-1 and ICAM-1 expression were greater in TRPV1−/−mice than WT mice. In addition, increased plasma calcitonin gene-related peptide (CGRP) levels observed in WT mice 6 h after LPS injection were absent in TRPV1−/−mice. Thus, TRPV1 ablation aggravates inflammatory responses, including neutrophil infiltration, proinflammatory cytokine production, and adhesion molecule expression, leading to intensified organ damage during endotoxic shock in the absence of worsened circulatory failure. The data indicate that TRPV1 activation may attenuate endotoxin-induced organ damage, possibly via its anti-inflammatory action rather than alteration of hemodynamics.

scholarly journals Mojabanchromanol Isolated from Sargassum horneri Attenuates Particulate Matter Induced Inflammatory Responses via Suppressing TLR2/4/7-MAPK Signaling in MLE-12 Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (7) ◽  
pp. 355
Author(s):  
Kalahe Hewage Iresha Nadeeka Madushani Herath ◽  
Hyo Jin Kim ◽  
Jae-Hyuk Jang ◽  
Hyun-Soo Kim ◽  
Hyun Jung Kim ◽  
...  
Keyword(s):  
Particulate Matter ◽  
Inflammatory Responses ◽  
Alveolar Epithelial Cell ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Sargassum Horneri ◽  
Mitogen Activated Protein Kinase ◽  
Epithelial Cell Line ◽  
Alveolar Epithelial ◽  
Mitogen Activated Protein

Chromanols from marine algae are studied for drug development due to its prominent bioactive properties, and mojabanchromanol (MC), a chromanol isolated from a brown algae Sargassum horneri, is found to possess anti-oxidant potential. In this study, we hypothesized MC may attenuate particulate matter (PM)-induced and reactive oxygen species (ROS)-mediated inflammatory responses in airways and tried to identify its potential and underlying mechanism against PM (majority <2.5 µm in diameter)-induced inflammatory responses in a lung type II alveolar epithelial cell line, MLE-12. MC attenuated PM-induced malondialdehyde (MDA), a lipid peroxidation end product, and 8-hydroxydeoxyguanosine (8-OHdG), the most representative DNA oxidative damage product, further validating MC’s potential in attenuating PM-induced oxidative stress. MC also suppressed PM-triggered TLR2/4/7 activation in MLE-12 cells. Moreover, MC reduced ROS-mediated phosphorylation of mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1/2 (Erk1/2) and c-Jun NH (2)-terminal kinase (JNK) that were also activated in PM exposed cells. MC further inhibited the secretion of pro-inflammatory cytokines (IL-6, IL-1β and IL-33) in MLE-12 cells exposed to PM. These results provide a clear evidence for MC’s potential in attenuating PM-triggered inflammatory responses in MLE-12 cells via repressing TLR2/4/7 and MAPK signaling. Therefore, MC can be developed as a therapeutic agent against PM induced airway inflammatory responses.

scholarly journals LPS promotes the progression of sepsis by activation of lncRNA HULC/miR-204-5p/TRPM7 network in HUVECs

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Xinghai Chen ◽  
Debiao Song
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Cell Viability ◽  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Receptor Potential ◽  
Luciferase Reporter ◽  
Inflammatory Injury ◽  
And Oxidative Stress

Abstract Sepsis is a systemic inflammatory response syndrome caused by infection. Lipopolysaccharide (LPS) has been reported to induce inflammatory responses, and long non-coding RNA highly up-regulated in liver cancer (HULC) expression was associated with the progression of sepsis. But the role and underlying mechanism of HULC in LPS-induced sepsis remain unclear. Cell viability and apoptosis were measured by methyl thiazolyl tetrazolium (MTT) and flow cytometry assays, respectively. The levels of apoptosis-related proteins, inflammatory cytokines and transient receptor potential melastatin7 (TRPM7) were detected by western blot. Reactive oxygen species (ROS), superoxide dismutase (SOD) and malondialdehyde (MDA) levels were detected by dichloro-dihydro-fluorescein diacetate (DCFH-DA) method using commercial kit. HULC, microRNA-204-5p (miR-204-5p) and TRPM7 expressions in serum of sepsis patients and human umbilical vein endothelial cells (HUVECs) were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were used to confirm the interaction between HULC and miR-204-5p, miR-204-5p and TRPM7. LPS stimulation restrained cell viability and facilitated apoptosis, inflammatory injury and oxidative stress in HUVECs. HULC and TRPM7 were increased and accompanied with decreased miR-204-5p expression in serum of sepsis patients. A significant negative correlation between miR-204-5p and HULC or TRPM7 was observed, and there was a positive relationship between expressions of HULC and TRPM7. Importantly, LPS inhibited the cell viability and induced apoptosis, inflammatory injury and oxidative stress of HUVECs by up-regulating the expressions of HULC and TRPM7, and down-modulating miR-204-5p expression. Mechanically, HULC positively regulated TRPM7 expression by sponging miR-204-5p in HUVECs. LPS impaired cell viability, and promoted cell apoptosis, inflammatory response and oxidative stress in HUVECs by regulating HULC/miR-204-5p/TRPM7 axis.

scholarly journals Role of the transient receptor potential vanilloid type 1 channel in renal inflammation induced by lipopolysaccharide in mice

2013 ◽  
Vol 304 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Youping Wang ◽  
Donna H. Wang
Keyword(s):  
Serum Creatinine ◽  
Transient Receptor Potential ◽  
Inflammatory Responses ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Renal Inflammation ◽  
Cytokine Levels ◽  
Transient Receptor

To determine the role of the transient receptor potential vanilloid type 1 (TRPV1) channel in the regulation of renal inflammation, lipopolysaccharide (LPS, 3 mg/kg) was intraperitoneally injected into wild-type (WT) and TRPV1-null mutant (TRPV1−/−) mice. The kidney and serum were collected 6 or 24 h after LPS injection for morphological analysis and proinflammatory cytokine assay. LPS injection led to a similar degree of transient hypotension and bradycardia in WT and TRPV1−/− mice determined by a telemetry system. LPS administration caused parenchymal red blood cell congestion and fading of intact glomerular structure in TRPV1−/− compared with WT mice. Serum creatinine levels were higher 24 h after LPS injection in TRPV1−/− than in WT mice. Neutrophil and macrophage infiltration in the kidneys was greater 6 h for the former and 24 h for both after LPS injection in TRPV1−/− than in WT mice. Serum cytokine levels including tumor necrosis factor (TNF)-α, IL-1β, and IL-6 were higher 6 h after LPS injection in TRPV1−/− compared with WT mice. Likewise, renal chemokine levels including keratinocyte-derived chemokines and macrophage inflammatory protein were higher 6 h after LPS injection in TRPV1−/− than in WT mice. Renal VCAM-1 and ICAM-1 expression was further elevated 6 h for the former and 24 h for the latter after LPS injection in TRPV1−/− than in WT mice. Renal nuclear factor-κB (NF-κB) activity was further increased 6 h after LPS injection in TRPV1−/− compared with WT mice. Pharmacological blockade TRPV1 in WT mice showed aggravated renal and serum inflammatory responses resembling that of TRPV1−/− mice. Thus TRPV1 gene ablation exacerbates LPS-induced renal tissue and function injury, including aggravated renal neutrophil and macrophage infiltration, chemokine and adhesion molecule levels, and glomerular hypercellularity accompanying with further increased serum creatinine and cytokine levels. These results indicate that TRPV1 is activated during LPS challenge, which may constitute a protect mechanism against LPS-induced renal injury via reducing renal inflammatory responses.

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