Serum level of hemokinin-1 is significantly lower in patients with chronic spontaneous urticaria than in healthy subjects

Nishimori, Nobuyuki; Toyoshima, Shota; Sasaki-Sakamoto, Tomomi; Hayama, Koremasa; Terada, Tadashi; Okayama, Yoshimichi

doi:10.1016/j.alit.2021.05.002

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…Intriguingly, the brief incubation of MCs with HK-1 caused the inhibition of histamine release and did not elicit rapid MRGPRX2 internalization. This suggests that, in healthy controls, HK-1 may regulate and desensitize MRGPRX2-mediated MC activation, thereby preventing MC degranulation by SP [86].…”

Section: Mrgprx2 Inhibitors-potential Therapeutic Candidatesmentioning

confidence: 97%

“…An example of this is Synta66, an inhibitor of the Orai channels, i.e., the calcium release-activated calcium channels in murine and human MCs, since, upon MRGPRX2-mediated activation of the inhibitor, an influx of Ca 2+ is induced [13,[83][84][85]. Taking an entirely different direction, the role of Hemokinin-1 (HK-1) in CU has also been investigated, as it was indicated to induce histamine release from LAD2 cells via MRGPRX2 in previous studies [86]. Higher serum levels of HK-1 were detected in healthy controls versus CU patients.…”

Section: Mrgprx2 Inhibitors-potential Therapeutic Candidatesmentioning

confidence: 99%

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Beyond Allergies—Updates on The Role of Mas-Related G-Protein-Coupled Receptor X2 in Chronic Urticaria and Atopic Dermatitis

Lerner,

Babina,

Zuberbier

et al. 2024

Cells

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Mast cells (MCs) are an important part of the immune system, responding both to pathogens and toxins, but they also play an important role in allergic diseases, where recent data show that non-IgE-mediated activation is also of relevance, especially in chronic urticaria (CU) and atopic dermatitis (AD). Skin MCs express Mas-related G-protein-coupled receptor X2 (MRGPRX2), a key protein in non-IgE-dependent MC degranulation, and its overactivity is one of the triggering factors for the above-mentioned diseases, making MRGPRX2 a potential therapeutic target. Reviewing the latest literature revealed our need to focus on the discovery of MRGPRX2 activators as well as the ongoing vast research towards finding specific MRGPRX2 inhibitors for potential therapeutic approaches. Most of these studies are in their preliminary stages, with one drug currently being investigated in a clinical trial. Future studies and improved model systems are needed to verify whether any of these inhibitors may have the potential to be the next therapeutic treatment for CU, AD, and other pseudo-allergic reactions.

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Section: Mrgprx2 Inhibitors-potential Therapeutic Candidatesmentioning

confidence: 97%

Section: Mrgprx2 Inhibitors-potential Therapeutic Candidatesmentioning

confidence: 99%

Beyond Allergies—Updates on The Role of Mas-Related G-Protein-Coupled Receptor X2 in Chronic Urticaria and Atopic Dermatitis

Lerner,

Babina,

Zuberbier

et al. 2024

Cells

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show abstract

“…HK4 is specifically expressed in the liver and pancreas (Shinkafi et al, 2020). Recent studies have shown that HK1 participates in the development of inflammation and immune regulation (Nishimori et al, 2021). However, whether HK1‐mediated glycolysis participates in the development of inflammation in AP and its mechanisms deserve to be explored.…”

Section: Introductionmentioning

confidence: 99%

Targeting hexokinase 1 alleviates NLRP3‐mediated inflammation in apical periodontitis: A laboratory investigation

et al. 2023

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Aim The aim of the study was to explore whether hexokinase 1 (HK1) is involved in the inhibition of inflammation mediated by nucleotide‐binding oligomerization domain‐like receptor protein 3 (NLRP3) signalling pathway in the development of apical periodontitis (AP). Methodology Human AP tissues and normal control tissues were collected in the clinic. First, the levels of glucose, pyruvate, lactate and hexokinase activity were examined in human AP tissues. ECAR and OCR were further measured to detect the level of glycolysis in vitro model of inflammation, which established with lipopolysaccharide (LPS)‐stimulated RAW264.7 cell line. Secondly, the expression of HK1, NLRP3, caspase‐1 and interleukin (IL)‐1β were measured by Western blot, immunohistochemistry or RT–qPCR. Finally, lentiviral short hairpin RNA (shRNA) silencing technique or the inhibitor 2‐deoxy‐d‐glucose (2‐DG) were used to further detect the relationship between HK1‐mediated glycolysis and NLRP3‐mediated inflammation in the development of AP in vitro. Results Initially, the level of glycolysis was significantly increased in human AP tissues. Subsequently, the expression of HK1, NLRP3, caspase‐1 and IL‐1β were upregulated significantly in human AP tissues. Furthermore, in the model of AP in vitro, a high level of glycolysis and the high expression of HK1, NLRP3, caspase‐1 and IL‐1β was observed. Finally, the expression of NLRP3, caspase‐1 and IL‐1β mediated by LPS stimulation was significantly reduced via HK1 knockdown or 2‐DG treatment in vitro. Conclusions Our data support that HK1‐mediated glycolysis plays a crucial role in the development of AP via upregulating the NLRP3 signalling pathway. Moreover, targeting HK1 may contribute to prevent the progression of AP, which has a potential clinical translation.

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Neuro-allergology: Mast cell–nerve cross-talk

Toyoshima

Okayama

2022

Allergology International

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Serum level of hemokinin-1 is significantly lower in patients with chronic spontaneous urticaria than in healthy subjects

Cited by 5 publications

References 18 publications

Beyond Allergies—Updates on The Role of Mas-Related G-Protein-Coupled Receptor X2 in Chronic Urticaria and Atopic Dermatitis

Beyond Allergies—Updates on The Role of Mas-Related G-Protein-Coupled Receptor X2 in Chronic Urticaria and Atopic Dermatitis

Targeting hexokinase 1 alleviates NLRP3‐mediated inflammation in apical periodontitis: A laboratory investigation

Neuro-allergology: Mast cell–nerve cross-talk

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