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Article ; Online: The contribution of mouse models to understanding atopic dermatitis.

Sanjel, Babina / Shim, Won-Sik

2022 Volume 203, Page(s) 115177

Abstract: Atopic dermatitis (AD) is a dermatological disease accompanied by dry and cracked skin with severe pruritus. Although various therapeutic strategies have been introduced to alleviate AD, it remains challenging to cure the disorder. To achieve such a goal, ...

Abstract	Atopic dermatitis (AD) is a dermatological disease accompanied by dry and cracked skin with severe pruritus. Although various therapeutic strategies have been introduced to alleviate AD, it remains challenging to cure the disorder. To achieve such a goal, understanding the pathophysiological mechanisms of AD is a prerequisite, requiring mouse models that properly reflect the AD phenotypes. Currently, numerous AD mouse models have been established, but each model has its own advantages and weaknesses. In this review, we categorized and summarized mouse models of AD and described their characteristics from a researcher's perspective.
MeSH term(s)	Animals ; Dermatitis, Atopic ; Disease Models, Animal ; Mice ; Skin
Language	English
Publishing date	2022-07-14
Publishing country	England
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	208787-x
ISSN	1873-2968 ; 0006-2952
ISSN (online)	1873-2968
ISSN	0006-2952
DOI	10.1016/j.bcp.2022.115177
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Article ; Online: Activation of serotonin receptor 2 by glucosylsphingosine can be enhanced by TRPA1 but not TRPV1: Implication of a novel glucosylsphingosine-mediated itch pathway.

Afzal, Ramsha / Shim, Won-Sik

Biochimica et biophysica acta. Biomembranes

2022 Volume 1864, Issue 11, Page(s) 184014

Abstract: Glucosylsphingosine (GS) is an endogenous sphingolipid that specifically accumulates in the skin of patients with atopic dermatitis (AD). Notably, it was recently found that GS can induce itch sensation by activating serotonin receptor 2A and TRPV4 ion ... ...

Abstract	Glucosylsphingosine (GS) is an endogenous sphingolipid that specifically accumulates in the skin of patients with atopic dermatitis (AD). Notably, it was recently found that GS can induce itch sensation by activating serotonin receptor 2A and TRPV4 ion channels. However, it is still uncertain whether other molecules are involved in GS-induced itch sensation. Therefore, by using the calcium imaging technique, we investigated whether serotonin receptor 2 - specifically 2A and 2B - can interact with TRPV1 and TRPA1, because these are representative ion channels in the transmission of itch. As a result, it was found that GS did not activate TRPV1 or TRPA1 per se. Moreover, cells expressing both serotonin receptor 2 and TRPV1 did not show any changes in calcium responses. However, enhanced calcium responses were observed in cells expressing serotonin receptor 2 and TRPA1, suggesting a possible interaction between these two molecules. Similar synergistic effects were also observed in cells expressing serotonin receptor 2 and TRPA1, but not TRPV1. Furthermore, a phospholipase C inhibitor (U73122) and a store-operated calcium entry blocker (SKF96365) significantly reduced GS-induced responses in cells expressing both serotonin receptor 2 and TRPA1, but not with pre-treatment with a Gβγ-complex blocker (gallein). Therefore, we propose a putative novel pathway for GS-induced itch sensation, such that serotonin receptor 2 could be coupled to TRPA1 but not TRPV1 in sensory neurons.
MeSH term(s)	Calcium/metabolism ; Humans ; Pruritus/metabolism ; Psychosine/analogs & derivatives ; Receptors, Serotonin/metabolism ; TRPA1 Cation Channel/metabolism ; TRPV Cation Channels ; Transient Receptor Potential Channels/physiology
Chemical Substances	Receptors, Serotonin ; TRPA1 Cation Channel ; TRPA1 protein, human ; TRPV Cation Channels ; TRPV1 protein, human ; Transient Receptor Potential Channels ; Psychosine (2238-90-6) ; sphingosyl beta-glucoside (52050-17-6) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2022-07-29
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	60-7
ISSN	1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2642 ; 1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbamem.2022.184014
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Article ; Online: Caffeic acid phenethyl ester inhibits pseudo-allergic reactions via inhibition of MRGPRX2/MrgprB2-dependent mast cell degranulation.

Adhikari, Nisha / Shim, Won-Sik

Archives of pharmacal research

2022 Volume 45, Issue 9, Page(s) 644–657

Abstract: Mast cells play essential role in allergic reactions through the process called mast cell degranulation. Recent studies have found that a basic secretagogue compound 48/80 (C48/80) induces non-IgE-mediated mast cell degranulation via activation of human ... ...

Abstract	Mast cells play essential role in allergic reactions through the process called mast cell degranulation. Recent studies have found that a basic secretagogue compound 48/80 (C48/80) induces non-IgE-mediated mast cell degranulation via activation of human Mas-related G protein-coupled receptor X2 (MRGPRX2) and mouse MrgprB2. Although previous studies have revealed that caffeic acid (CA) and its derivatives possess anti-allergic effects via IgE-dependent manner, it is largely elusive whether these compounds have impact on MRGPRX2/MrgprB2 to exert inhibitory effects. Therefore, the present study investigated whether CA as well as its derivatives - rosmarinic acid (RA) and caffeic acid phenethyl ester (CAPE) - has the ability to inhibit the activity of MRGPRX2/MrgprB2 to evoke pseudo-allergic effects. As a result, it was found that CAPE inhibits C48/80-induced activation of MRGPRX2/MrgprB2, but neither CA nor RA showed discernible inhibition. Furthermore, the β-hexosaminidase release assay showed that CAPE inhibits mouse peritoneal mast cell degranulation in both IgE-dependent and MrgprB2-dependent manners. Additionally, mouse paw edema induced by C48/80 was dramatically suppressed by co-treatment of CAPE, suggesting that CAPE possesses a protective effect on C48/80-evoked pseudo-allergic reactions. The pretreatment of CAPE also significantly decreased scratching bouts of mice evoked by C48/80, demonstrating that CAPE also has an anti-pruritic effect. Therefore, these data implicate that CAPE can suppress pseudo-allergic reactions evoked by C48/80 via MrgprB2-dependent manner. Finally, molecular docking analysis showed that CAPE is predicted to bind to human MRGPRX2 in the region where C48/80 also binds, implying that CAPE can be a competitive inhibitor of MRGPRX2. In conclusion, it is found that CAPE has the ability to inhibit MRGPRX2/MrgprB2, leading to the prevention of mast cell degranulation and further to the alleviation of mast cell reactions. These results indicate that CAPE as a CA derivative could be developed as a new protective agent that exerts dual inhibition of mast cell degranulation mediated by IgE and MRGPRX2/MrgprB2.
MeSH term(s)	Animals ; Anti-Allergic Agents/pharmacology ; Caffeic Acids ; Cell Degranulation ; Humans ; Hypersensitivity ; Mast Cells ; Mice ; Mice, Inbred C57BL ; Molecular Docking Simulation ; Nerve Tissue Proteins/metabolism ; Nerve Tissue Proteins/pharmacology ; Phenylethyl Alcohol/analogs & derivatives ; Receptors, G-Protein-Coupled/metabolism ; Receptors, Neuropeptide/metabolism ; Secretagogues/metabolism ; Secretagogues/pharmacology ; beta-N-Acetylhexosaminidases/metabolism ; beta-N-Acetylhexosaminidases/pharmacology ; p-Methoxy-N-methylphenethylamine/metabolism ; p-Methoxy-N-methylphenethylamine/pharmacology
Chemical Substances	Anti-Allergic Agents ; Caffeic Acids ; MRGPRX2 protein, human ; Mrgprb2 protein, mouse ; Nerve Tissue Proteins ; Receptors, G-Protein-Coupled ; Receptors, Neuropeptide ; Secretagogues ; p-Methoxy-N-methylphenethylamine (4091-50-3) ; beta-N-Acetylhexosaminidases (EC 3.2.1.52) ; caffeic acid phenethyl ester (G960R9S5SK) ; Phenylethyl Alcohol (ML9LGA7468) ; caffeic acid (U2S3A33KVM)
Language	English
Publishing date	2022-10-02
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	447623-2
ISSN	1976-3786 ; 0253-6269
ISSN (online)	1976-3786
ISSN	0253-6269
DOI	10.1007/s12272-022-01405-2
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Article: Lithocholic Acid Activates Mas-Related G Protein-Coupled Receptors, Contributing to Itch in Mice.

Song, Myung-Hyun / Shim, Won-Sik

Biomolecules & therapeutics

2021 Volume 30, Issue 1, Page(s) 38–47

Abstract: The present study focused on lithocholic acid (LCA), a secondary bile acid that contributes to cholestatic pruritus. Although recent studies have found that LCA acts on MAS-related G protein-coupled receptor family member X4 (MRGPRX4) in humans, it is ... ...

Abstract	The present study focused on lithocholic acid (LCA), a secondary bile acid that contributes to cholestatic pruritus. Although recent studies have found that LCA acts on MAS-related G protein-coupled receptor family member X4 (MRGPRX4) in humans, it is unclear which subtypes of MRGPRs are activated by LCA in mice since there is no precise ortholog of human MRGPRX4 in the mouse genome. Using calcium imaging, we found that LCA could activate mouse Mrgpra1 when transiently expressed in HEK293T cells. Moreover, LCA similarly activates mouse Mrgprb2. Importantly, LCA-induced responses showed dose-dependent effects through Mrgpra1 and Mrgprb2. Moreover, treatment with QWF (an antagonist of Mrgpra1 and Mrgprb2), YM254890 (Gα
Language	English
Publishing date	2021-07-14
Publishing country	Korea (South)
Document type	Journal Article
ZDB-ID	2734146-X
ISSN	2005-4483 ; 1976-9148
ISSN (online)	2005-4483
ISSN	1976-9148
DOI	10.4062/biomolther.2021.059
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Article ; Online: Caffeic acid phenethyl ester inhibits pseudo-allergic reactions via inhibition of MRGPRX2/MrgprB2-dependent mast cell degranulation

Adhikari, Nisha / Shim, Won-Sik

Arch. Pharm. Res.. 2022 Sept., v. 45, no. 9 p.644-657

2022

Abstract	Mast cells play essential role in allergic reactions through the process called mast cell degranulation. Recent studies have found that a basic secretagogue compound 48/80 (C48/80) induces non-IgE-mediated mast cell degranulation via activation of human Mas-related G protein-coupled receptor X2 (MRGPRX2) and mouse MrgprB2. Although previous studies have revealed that caffeic acid (CA) and its derivatives possess anti-allergic effects via IgE-dependent manner, it is largely elusive whether these compounds have impact on MRGPRX2/MrgprB2 to exert inhibitory effects. Therefore, the present study investigated whether CA as well as its derivatives – rosmarinic acid (RA) and caffeic acid phenethyl ester (CAPE) – has the ability to inhibit the activity of MRGPRX2/MrgprB2 to evoke pseudo-allergic effects. As a result, it was found that CAPE inhibits C48/80-induced activation of MRGPRX2/MrgprB2, but neither CA nor RA showed discernible inhibition. Furthermore, the β-hexosaminidase release assay showed that CAPE inhibits mouse peritoneal mast cell degranulation in both IgE-dependent and MrgprB2-dependent manners. Additionally, mouse paw edema induced by C48/80 was dramatically suppressed by co-treatment of CAPE, suggesting that CAPE possesses a protective effect on C48/80-evoked pseudo-allergic reactions. The pretreatment of CAPE also significantly decreased scratching bouts of mice evoked by C48/80, demonstrating that CAPE also has an anti-pruritic effect. Therefore, these data implicate that CAPE can suppress pseudo-allergic reactions evoked by C48/80 via MrgprB2-dependent manner. Finally, molecular docking analysis showed that CAPE is predicted to bind to human MRGPRX2 in the region where C48/80 also binds, implying that CAPE can be a competitive inhibitor of MRGPRX2. In conclusion, it is found that CAPE has the ability to inhibit MRGPRX2/MrgprB2, leading to the prevention of mast cell degranulation and further to the alleviation of mast cell reactions. These results indicate that CAPE as a CA derivative could be developed as a new protective agent that exerts dual inhibition of mast cell degranulation mediated by IgE and MRGPRX2/MrgprB2.
Keywords	G-protein coupled receptors ; anti-allergic agents ; caffeic acid ; edema ; humans ; mast cells ; mice ; protective effect ; rosmarinic acid
Language	English
Dates of publication	2022-09
Size	p. 644-657.
Publishing place	Pharmaceutical Society of Korea
Document type	Article ; Online
ZDB-ID	447623-2
ISSN	1976-3786 ; 0253-6269
ISSN (online)	1976-3786
ISSN	0253-6269
DOI	10.1007/s12272-022-01405-2
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Article ; Online: Cutaneous Neuroimmune Interactions of TSLP and TRPV4 Play Pivotal Roles in Dry Skin-Induced Pruritus.

Lee, Wook-Joo / Shim, Won-Sik

Frontiers in immunology

2021 Volume 12, Page(s) 772941

Abstract: Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced ... ...

Abstract	Dry skin is a symptom of skin barrier dysfunction that evokes pruritus; however, the cutaneous neuroimmune interactions underlying dry skin-induced pruritus remain unclear. Therefore, we aimed to elucidate the mechanisms underlying dry skin-induced pruritus. To this end, an acetone/ethanol/water (AEW)-induced mouse model of dry skin was used in this study. We observed that the production of thymic stromal lymphopoietin (TSLP) significantly increased in the keratinocytes of AEW mice. Importantly, treatment with an antagonist of transient receptor potential cation channel subfamily V member 4 (TRPV4), HC067047, ameliorated dry skin conditions in AEW mice. The symptoms of dry skin were significantly reduced in
MeSH term(s)	Animals ; Cells, Cultured ; Cytokines/immunology ; Ganglia, Spinal ; Humans ; Keratinocytes/immunology ; Male ; Mast Cells/immunology ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Knockout ; Morpholines/pharmacology ; Neuroimmunomodulation ; Neurons/immunology ; Pruritus/immunology ; Pyrroles/pharmacology ; Skin/immunology ; TRPV Cation Channels/antagonists & inhibitors ; TRPV Cation Channels/genetics ; TRPV Cation Channels/immunology ; Thymic Stromal Lymphopoietin ; Mice
Chemical Substances	Cytokines ; HC-067047 ; Morpholines ; Pyrroles ; TRPV Cation Channels ; Trpv4 protein, mouse ; Thymic Stromal Lymphopoietin (GT0IL38SP4)
Language	English
Publishing date	2021-12-02
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.772941
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Article ; Online: A phytosphingosine derivative mYG-II-6 inhibits histamine-mediated TRPV1 activation and MRGPRX2-dependent mast cell degranulation.

Adhikari, Nisha / Lee, Wook-Joo / Park, Soojun / Kim, Sanghee / Shim, Won-Sik

International immunopharmacology

2024 Volume 133, Page(s) 112113

Abstract: Background: Phytosphingosine and its derivative are known for their skin-protective properties. While mYG-II-6, a phytosphingosine derivative, has shown anti-inflammatory and antipsoriatic effects, its potential antipruritic qualities have yet to be ... ...

Abstract	Background: Phytosphingosine and its derivative are known for their skin-protective properties. While mYG-II-6, a phytosphingosine derivative, has shown anti-inflammatory and antipsoriatic effects, its potential antipruritic qualities have yet to be explored. This study aimed to investigate mYG-II-6's antipruritic properties. Methods: The calcium imaging technique was employed to investigate the activity of ion channels and receptors. Mast cell degranulation was confirmed through the β-hexosaminidase assay. Additionally, in silico molecular docking and an in vivo mouse scratching behavior test were utilized. Results: Using HEK293T cells transfected with H1R and TRPV1, we examined the impact of mYG-II-6 on histamine-induced intracellular calcium rise, a key signal in itch-mediating sensory neurons. Pretreatment with mYG-II-6 significantly reduced histamine-induced calcium levels and inhibited TRPV1 activity, suggesting its role in blocking the calcium influx channel. Additionally, mYG-II-6 suppressed histamine-induced calcium increase in primary cultures of mouse dorsal root ganglia, indicating its potential antipruritic effect mediated by histamine. Interestingly, mYG-II-6 exhibited inhibitory effects on human MRGPRX2, a G protein-coupled receptor involved in IgE-independent mast cell degranulation. However, it did not inhibit mouse MrgprB2, the ortholog of human MRGPRX2. Molecular docking analysis revealed that mYG-II-6 selectively interacts with the binding pocket of MRGPRX2. Importantly, mYG-II-6 suppressed histamine-induced scratching behaviors in mice. Conclusions: Our findings show that mYG-II-6 can alleviate histamine-induced itch sensation through dual mechanisms. This underscores its potential as a versatile treatment for various pruritic conditions.
Language	English
Publishing date	2024-04-23
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2043785-7
ISSN	1878-1705 ; 1567-5769
ISSN (online)	1878-1705
ISSN	1567-5769
DOI	10.1016/j.intimp.2024.112113
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Article ; Online: Recent advances in understanding the molecular mechanisms of cholestatic pruritus: A review.

Sanjel, Babina / Shim, Won-Sik

Biochimica et biophysica acta. Molecular basis of disease

2020 Volume 1866, Issue 12, Page(s) 165958

Abstract: Cholestasis, a condition characterized by an abnormal decrease in bile flow, is accompanied by various symptoms such as pruritus. Although cholestatic pruritus is a prominent condition, its precise mechanisms have largely been elusive. Recently, ... ...

Abstract	Cholestasis, a condition characterized by an abnormal decrease in bile flow, is accompanied by various symptoms such as pruritus. Although cholestatic pruritus is a prominent condition, its precise mechanisms have largely been elusive. Recently, advancements have been made for understanding the etiology and pathogenesis of cholestatic pruritus. The current review therefore focuses on summarizing the overall progress made in the elucidation of its molecular mechanisms. We have reviewed the available animal models on cholestasis to compare the differences between them, characterized potential pruritogens involved in cholestatic pruritus, and have summarized the receptor and ion channels implicated in the condition. Finally, we have discussed the available treatment options for alleviation of cholestatic pruritus. As our understanding of the mechanisms of cholestatic pruritus deepens, novel strategies to cure this condition are awaited.
MeSH term(s)	Animals ; Cholestasis/metabolism ; Cholestasis/pathology ; Humans ; Pruritus/metabolism ; Pruritus/pathology
Language	English
Publishing date	2020-09-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-260X ; 1879-2596 ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 0304-419X ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbadis.2020.165958
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Article ; Online: Synthesis of Graphitic Carbon Coated ZnPS

Kim, Hyung-Ho / Lee, Eungjae / Kim, Kyeong-Ho / Shim, Hun / Lee, Jongwon / Lee, Dongjun / Lee, Doyeon / Kim, Won-Sik / Hong, Seong-Hyeon

Small methods

2023 Volume 8, Issue 3, Page(s) e2301294

Abstract: Graphitic carbon-coated ... ...

Abstract	Graphitic carbon-coated ZnPS
Language	English
Publishing date	2023-11-21
Publishing country	Germany
Document type	Journal Article
ISSN	2366-9608
ISSN (online)	2366-9608
DOI	10.1002/smtd.202301294
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Article ; Online: Development of a Novel Blue Fluorescent Gene-encoded Calcium Indicator Modified from GCaMP3.

Yum, Chorok / Ahn, Taekyoung / Shim, Won-Sik

Journal of fluorescence

2020 Volume 30, Issue 6, Page(s) 1287–1293

Abstract: Intracellular calcium can be monitored by various calcium-specific fluorescent dyes including gene-encoded calcium indicators (GECI). GCaMP is a widely-used GECI that emits green fluorescence proportional to the level of intracellular calcium. However, ... ...

Abstract	Intracellular calcium can be monitored by various calcium-specific fluorescent dyes including gene-encoded calcium indicators (GECI). GCaMP is a widely-used GECI that emits green fluorescence proportional to the level of intracellular calcium. However, since many tagging proteins also emit green fluorescence, GCaMP cannot be used with another green fluorescent protein. Therefore, it would be ideal to develop a GECI that has a distinct color profile other than green. In this regard, we developed a novel blue fluorescent calcium indicator modified from GCaMP called Ser
MeSH term(s)	Amino Acid Substitution ; Calcium/metabolism ; Color ; Fluorescence ; HEK293 Cells ; Humans ; Intracellular Space/metabolism ; Luminescent Proteins/genetics ; Luminescent Proteins/metabolism ; Temperature
Chemical Substances	Luminescent Proteins ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2020-08-24
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2016892-5
ISSN	1573-4994 ; 1053-0509
ISSN (online)	1573-4994
ISSN	1053-0509
DOI	10.1007/s10895-020-02606-y
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