Increased cis-to-trans urocanic acid ratio in the skin of chronic spontaneous urticaria patients

Duy Le Pham; Kyung Min Lim; Kyung Mi Joo; Hae Sim Park; Donald Y.M. Leung; Young Min Ye

doi:10.1038/s41598-017-01487-9

Increased cis-to-trans urocanic acid ratio in the skin of chronic spontaneous urticaria patients

Duy Le Pham, Kyung Min Lim, Kyung Mi Joo, Hae Sim Park, Donald Y.M. Leung, Young Min Ye

Department of Pharmaceutical Sciences

Research output: Contribution to journal › Article › peer-review

10 Scopus citations

Abstract

Increased filaggrin expression was found to be correlated with severity scores in chronic spontaneous urticaria (CSU); however, the role of filaggrin breakdown products (FBPs) in CSU has not been studied. We collected stratum corneum (SC) specimens from the volar forearms of 10 CSU patients, 10 AD patients, and 10 healthy normal controls (NCs) and measured contents of FBPs (pyrrolidone carboxylic acid [PCA] and urocanic acid [UCA]) using UPLC-MS/MS, transepidermal water loss (TEWL) and epidermal pH. Compared to NCs, cis-UCA level was increased in CSU lesions (P < 0.05) and decreased in AD lesions (P < 0.01). The cis-to-trans-UCA ratio in SC specimens from CSU patients was significantly greater than those from AD and NC subjects. AD lesions had lower FBP and PCA contents compared to NC skin (both P < 0.001), and higher TEWL and pH compared to CSU lesions. Moreover, cis-UCA, but not trans-UCA, enhanced the IgE-mediated basophil activation, as well as IgE- A nd calcium-mediated degranulation of LAD-2 cells, in a dose-dependent manner. These findings suggest that increased cis-to-trans UCA ratio in the epidermis is a distinct feature of CSU, which could enhance mast cell degranulation. Modulation of cis-UCA may be a potential target for skin diseases associated with IgE-mediated mast cell degranulation.

Original language	English
Article number	1318
Journal	Scientific Reports
Volume	7
Issue number	1
DOIs	https://doi.org/10.1038/s41598-017-01487-9
State	Published - 1 Dec 2017

Bibliographical note

Funding Information:
This work was supported by grants from the National Research Foundation of Korea, funded by the Korean Government (MSIP: NRF-2012R1A5A2048183).

Publisher Copyright:
© 2017 The Author(s).

Access to Document

10.1038/s41598-017-01487-9

Cite this

@article{0229550acdb1482f8df874b95d34133f,

title = "Increased cis-to-trans urocanic acid ratio in the skin of chronic spontaneous urticaria patients",

abstract = "Increased filaggrin expression was found to be correlated with severity scores in chronic spontaneous urticaria (CSU); however, the role of filaggrin breakdown products (FBPs) in CSU has not been studied. We collected stratum corneum (SC) specimens from the volar forearms of 10 CSU patients, 10 AD patients, and 10 healthy normal controls (NCs) and measured contents of FBPs (pyrrolidone carboxylic acid [PCA] and urocanic acid [UCA]) using UPLC-MS/MS, transepidermal water loss (TEWL) and epidermal pH. Compared to NCs, cis-UCA level was increased in CSU lesions (P < 0.05) and decreased in AD lesions (P < 0.01). The cis-to-trans-UCA ratio in SC specimens from CSU patients was significantly greater than those from AD and NC subjects. AD lesions had lower FBP and PCA contents compared to NC skin (both P < 0.001), and higher TEWL and pH compared to CSU lesions. Moreover, cis-UCA, but not trans-UCA, enhanced the IgE-mediated basophil activation, as well as IgE- A nd calcium-mediated degranulation of LAD-2 cells, in a dose-dependent manner. These findings suggest that increased cis-to-trans UCA ratio in the epidermis is a distinct feature of CSU, which could enhance mast cell degranulation. Modulation of cis-UCA may be a potential target for skin diseases associated with IgE-mediated mast cell degranulation.",

author = "Pham, {Duy Le} and Lim, {Kyung Min} and Joo, {Kyung Mi} and Park, {Hae Sim} and Leung, {Donald Y.M.} and Ye, {Young Min}",

note = "Funding Information: This work was supported by grants from the National Research Foundation of Korea, funded by the Korean Government (MSIP: NRF-2012R1A5A2048183). Publisher Copyright: {\textcopyright} 2017 The Author(s).",

year = "2017",

month = dec,

day = "1",

doi = "10.1038/s41598-017-01487-9",

language = "English",

volume = "7",

journal = "Scientific Reports",

issn = "2045-2322",

publisher = "Nature Publishing Group",

number = "1",

}

TY - JOUR

T1 - Increased cis-to-trans urocanic acid ratio in the skin of chronic spontaneous urticaria patients

AU - Pham, Duy Le

AU - Lim, Kyung Min

AU - Joo, Kyung Mi

AU - Park, Hae Sim

AU - Leung, Donald Y.M.

AU - Ye, Young Min

N1 - Funding Information: This work was supported by grants from the National Research Foundation of Korea, funded by the Korean Government (MSIP: NRF-2012R1A5A2048183). Publisher Copyright: © 2017 The Author(s).

PY - 2017/12/1

Y1 - 2017/12/1

N2 - Increased filaggrin expression was found to be correlated with severity scores in chronic spontaneous urticaria (CSU); however, the role of filaggrin breakdown products (FBPs) in CSU has not been studied. We collected stratum corneum (SC) specimens from the volar forearms of 10 CSU patients, 10 AD patients, and 10 healthy normal controls (NCs) and measured contents of FBPs (pyrrolidone carboxylic acid [PCA] and urocanic acid [UCA]) using UPLC-MS/MS, transepidermal water loss (TEWL) and epidermal pH. Compared to NCs, cis-UCA level was increased in CSU lesions (P < 0.05) and decreased in AD lesions (P < 0.01). The cis-to-trans-UCA ratio in SC specimens from CSU patients was significantly greater than those from AD and NC subjects. AD lesions had lower FBP and PCA contents compared to NC skin (both P < 0.001), and higher TEWL and pH compared to CSU lesions. Moreover, cis-UCA, but not trans-UCA, enhanced the IgE-mediated basophil activation, as well as IgE- A nd calcium-mediated degranulation of LAD-2 cells, in a dose-dependent manner. These findings suggest that increased cis-to-trans UCA ratio in the epidermis is a distinct feature of CSU, which could enhance mast cell degranulation. Modulation of cis-UCA may be a potential target for skin diseases associated with IgE-mediated mast cell degranulation.

AB - Increased filaggrin expression was found to be correlated with severity scores in chronic spontaneous urticaria (CSU); however, the role of filaggrin breakdown products (FBPs) in CSU has not been studied. We collected stratum corneum (SC) specimens from the volar forearms of 10 CSU patients, 10 AD patients, and 10 healthy normal controls (NCs) and measured contents of FBPs (pyrrolidone carboxylic acid [PCA] and urocanic acid [UCA]) using UPLC-MS/MS, transepidermal water loss (TEWL) and epidermal pH. Compared to NCs, cis-UCA level was increased in CSU lesions (P < 0.05) and decreased in AD lesions (P < 0.01). The cis-to-trans-UCA ratio in SC specimens from CSU patients was significantly greater than those from AD and NC subjects. AD lesions had lower FBP and PCA contents compared to NC skin (both P < 0.001), and higher TEWL and pH compared to CSU lesions. Moreover, cis-UCA, but not trans-UCA, enhanced the IgE-mediated basophil activation, as well as IgE- A nd calcium-mediated degranulation of LAD-2 cells, in a dose-dependent manner. These findings suggest that increased cis-to-trans UCA ratio in the epidermis is a distinct feature of CSU, which could enhance mast cell degranulation. Modulation of cis-UCA may be a potential target for skin diseases associated with IgE-mediated mast cell degranulation.

UR - http://www.scopus.com/inward/record.url?scp=85018277002&partnerID=8YFLogxK

U2 - 10.1038/s41598-017-01487-9

DO - 10.1038/s41598-017-01487-9

M3 - Article

C2 - 28465560

AN - SCOPUS:85018277002

SN - 2045-2322

VL - 7

JO - Scientific Reports

JF - Scientific Reports

IS - 1

M1 - 1318

ER -

Increased cis-to-trans urocanic acid ratio in the skin of chronic spontaneous urticaria patients

Abstract

Bibliographical note

Access to Document

Fingerprint

Cite this