scholarly journals The Roles of Transient Receptor Potential Vanilloid 1 and 4 in Pneumococcal Nasal Colonization and Subsequent Development of Invasive Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Masamitsu Kono ◽  
Denisa Nanushaj ◽  
Hideki Sakatani ◽  
Daichi Murakami ◽  
Masayoshi Hijiya ◽  
...  

Transient receptor potential (TRP) channels, neuronal stimulations widely known to be associated with thermal responses, pain induction, and osmoregulation, have been shown in recent studies to have underlying mechanisms associated with inflammatory responses. The role of TRP channels on inflammatory milieu during bacterial infections has been widely demonstrated. It may vary among types of channels/pathogens, however, and it is not known how TRP channels function during pneumococcal infections. Streptococcus pneumoniae can cause severe infections such as pneumonia, bacteremia, and meningitis, with systemic inflammatory responses. This study examines the role of TRP channels (TRPV1 and TRPV4) for pneumococcal nasal colonization and subsequent development of invasive pneumococcal disease in a mouse model. Both TRPV1 and TRPV4 channels were shown to be related to regulation of the development of pneumococcal diseases. In particular, the influx of neutrophils (polymorphonuclear cells) in the nasal cavity and the bactericidal activity were significantly suppressed among TRPV4 knockout mice. This may lead to severe pneumococcal pneumonia, resulting in dissemination of the bacteria to various organs and causing high mortality during influenza virus coinfection. Regulating host immune responses by TRP channels could be a novel strategy against pathogenic microorganisms causing strong local/systemic inflammation.

2013 ◽  
Vol 304 (1) ◽  
pp. R1-R9 ◽  
Author(s):  
Youping Wang ◽  
Donna H. Wang

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.


Cancers ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 322 ◽  
Author(s):  
Giorgio Santoni ◽  
Consuelo Amantini

Recently, the finding of cancer stem cells in brain tumors has increased the possibilitiesfor advancing new therapeutic approaches with the aim to overcome the limits of current availabletreatments. In addition, a role for ion channels, particularly of TRP channels, in developing neuronsas well as in brain cancer development and progression have been demonstrated. Herein, we focuson the latest advancements in understanding the role of TRPV2, a Ca2+ permeable channel belongingto the TRPV subfamily in neurogenesis and gliomagenesis. TRPV2 has been found to be expressedin both neural progenitor cells and glioblastoma stem/progenitor-like cells (GSCs). In developingneurons, post-translational modifications of TRPV2 (e.g., phosphorylation by ERK2) are required tostimulate Ca2+ signaling and nerve growth factor-mediated neurite outgrowth. TRPV2overexpression also promotes GSC differentiation and reduces gliomagenesis in vitro and in vivo.In glioblastoma, TRPV2 inhibits survival and proliferation, and induces Fas/CD95-dependentapoptosis. Furthermore, by proteomic analysis, the identification of a TRPV2 interactome-basedsignature and its relation to glioblastoma progression/recurrence, high or low overall survival anddrug resistance strongly suggest an important role of the TRPV2 channel as a potential biomarkerin glioblastoma prognosis and therapy.


2021 ◽  
Vol 22 (7) ◽  
pp. 3360
Author(s):  
Mee-Ra Rhyu ◽  
Yiseul Kim ◽  
Vijay Lyall

In addition to the sense of taste and olfaction, chemesthesis, the sensation of irritation, pungency, cooling, warmth, or burning elicited by spices and herbs, plays a central role in food consumption. Many plant-derived molecules demonstrate their chemesthetic properties via the opening of transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) channels. TRPA1 and TRPV1 are structurally related thermosensitive cation channels and are often co-expressed in sensory nerve endings. TRPA1 and TRPV1 can also indirectly influence some, but not all, primary taste qualities via the release of substance P and calcitonin gene-related peptide (CGRP) from trigeminal neurons and their subsequent effects on CGRP receptor expressed in Type III taste receptor cells. Here, we will review the effect of some chemesthetic agonists of TRPA1 and TRPV1 and their influence on bitter, sour, and salt taste qualities.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 334
Author(s):  
Huilong Luo ◽  
Xavier Declèves ◽  
Salvatore Cisternino

The gliovascular unit (GVU) is composed of the brain microvascular endothelial cells forming blood–brain barrier and the neighboring surrounding “mural” cells (e.g., pericytes) and astrocytes. Modulation of the GVU/BBB features could be observed in a variety of vascular, immunologic, neuro-psychiatric diseases, and cancers, which can disrupt the brain homeostasis. Ca2+ dynamics have been regarded as a major factor in determining BBB/GVU properties, and previous studies have demonstrated the role of transient receptor potential vanilloid (TRPV) channels in modulating Ca2+ and BBB/GVU properties. The physiological role of thermosensitive TRPV channels in the BBB/GVU, as well as their possible therapeutic potential as targets in treating brain diseases via preserving the BBB are reviewed. TRPV2 and TRPV4 are the most abundant isoforms in the human BBB, and TRPV2 was evidenced to play a main role in regulating human BBB integrity. Interspecies differences in TRPV2 and TRPV4 BBB expression complicate further preclinical validation. More studies are still needed to better establish the physiopathological TRPV roles such as in astrocytes, vascular smooth muscle cells, and pericytes. The effect of the chronic TRPV modulation should also deserve further studies to evaluate their benefit and innocuity in vivo.


Author(s):  
Sanjeev K. Singh ◽  
M. S. Muthu ◽  
Ravindran Revand ◽  
M. B. Mandal

Background: Since long back, it has been a matter of discussion regarding the role of peripheral blood vessels in regulation of cardiorespiratory (CVR) system. Objective: The role of 5-HT3 and TRPV1 receptors present on perivascular nerves in elicitation of CVR reflexes was examined after intra-arterial instillation of bradykinin in urethane anesthetized rats. Materials and Methods: Femoral artery was cannulated retrogradely and was utilized for the instillation of saline/agonist/antagonist and recording of blood pressure (BP), using a double ported 24G cannula. BP, respiration and ECG were recorded for 30 min after bradykinin (1 µM) in the absence or presence of antagonists. Results: Instillation of bradykinin produced immediate hypotensive (40%), bradycardiac (17%), tachypnoeic (45%) and hyperventilatory (96%) responses of shorter latencies (5-8 s) favoring the neural mechanisms in producing the responses. In lignocaine (2%) pretreated animals, bradykinin-induced hypotensive (10%), bradycardiac (1.7%), tachypnoeic (13%) and hyperventilatory (13%) responses attenuated significantly. Pretreatment with ondansetron (100 µg/kg), 5-HT3-antagonist attenuated the hypotensive (10%), bradycardiac (1.7%), tachypnoeic (11%) and hyperventilatory (11%) responses significantly. Pretreatment with capsazepine (1 mg/kg), transient receptor potential vanilloid 1- antagonist blocked the hypotensive (5%), bradycardiac (1.2%), tachypnoeic (6%) and hyperventilatory (6%) responses significantly. Conclusion: In conclusion, presence of a nociceptive agent in the local segment of an artery evokes vasosensory reflex responses modulating CVR parameters involving TRPV1 and 5-HT3 receptors present on the perivascular sensory nerve terminals in anesthetized rats.


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