Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction

Chiang Wen Lee, Zih Chan Lin, Stephen Chu Sung Hu, Yao Chang Chiang, Lee Fen Hsu, Yu Ching Lin, I-Ta Lee, Ming Horng Tsai, Jia You Fang

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.

Original languageEnglish
Article number27995
JournalScientific Reports
Volume6
DOIs
Publication statusPublished - Jun 17 2016
Externally publishedYes

Fingerprint

Particulate Matter
Cyclooxygenase 2
Dinoprostone
Down-Regulation
Aryl Hydrocarbon Receptors
Skin
Reactive Oxygen Species
NADPH Oxidase
Transcription Factor AP-1
Prostaglandin Receptors
Cyclooxygenase 2 Inhibitors
Keratinocytes
Transfection
filaggrin
Anti-Inflammatory Agents
Antioxidants
Phosphorylation

ASJC Scopus subject areas

  • General

Cite this

Lee, C. W., Lin, Z. C., Hu, S. C. S., Chiang, Y. C., Hsu, L. F., Lin, Y. C., ... Fang, J. Y. (2016). Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction. Scientific Reports, 6, [27995]. https://doi.org/10.1038/srep27995

Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction. / Lee, Chiang Wen; Lin, Zih Chan; Hu, Stephen Chu Sung; Chiang, Yao Chang; Hsu, Lee Fen; Lin, Yu Ching; Lee, I-Ta; Tsai, Ming Horng; Fang, Jia You.

In: Scientific Reports, Vol. 6, 27995, 17.06.2016.

Research output: Contribution to journalArticle

Lee, Chiang Wen ; Lin, Zih Chan ; Hu, Stephen Chu Sung ; Chiang, Yao Chang ; Hsu, Lee Fen ; Lin, Yu Ching ; Lee, I-Ta ; Tsai, Ming Horng ; Fang, Jia You. / Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction. In: Scientific Reports. 2016 ; Vol. 6.
@article{c2a400f79cfc4230925b96e40376e67e,
title = "Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction",
abstract = "We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.",
author = "Lee, {Chiang Wen} and Lin, {Zih Chan} and Hu, {Stephen Chu Sung} and Chiang, {Yao Chang} and Hsu, {Lee Fen} and Lin, {Yu Ching} and I-Ta Lee and Tsai, {Ming Horng} and Fang, {Jia You}",
year = "2016",
month = "6",
day = "17",
doi = "10.1038/srep27995",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Urban particulate matter down-regulates filaggrin via COX2 expression/PGE2 production leading to skin barrier dysfunction

AU - Lee, Chiang Wen

AU - Lin, Zih Chan

AU - Hu, Stephen Chu Sung

AU - Chiang, Yao Chang

AU - Hsu, Lee Fen

AU - Lin, Yu Ching

AU - Lee, I-Ta

AU - Tsai, Ming Horng

AU - Fang, Jia You

PY - 2016/6/17

Y1 - 2016/6/17

N2 - We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.

AB - We explored the regulation of filaggrin, cyclooxygenase 2 (COX2) and prostaglandin E2 (PGE2) expression induced by urban particulate matter (PM) in human keratinocytes. In addition, we investigated the signaling pathways involved in PM-induced effects on COX2/PGE2 and filaggrin. PMs induced increases in COX2 expression and PGE2 production, and decreased filaggrin expression. These effects were attenuated by pretreatment with COX2 inhibitor and PGE2 receptor antagonist, or after transfection with siRNAs of the aryl hydrocarbon receptor (AhR), gp91phox and p47phox. Furthermore, PM-induced generation of reactive oxygen species (ROS) and NADPH oxidase activity was attenuated by pretreatment with an AhR antagonist (AhRI) or antioxidants. Moreover, Nox-dependent ROS generation led to phosphorylation of ERK1/2, p38, and JNK, which then activated the downstream molecules NF-κB and AP-1, respectively. In vivo studies in PMs-treated mice showed that AhRI and apocynin (a Nox2 inhibitor) had anti-inflammatory effects by decreasing COX2 and increasing filaggrin expression. Our results reveal for the first time that PMs-induced ROS generation is mediated through the AhR/p47 phox/NADPH oxidase pathway, which in turn activates ERK1/2, p38/NF-κB and JNK/AP-1, and which ultimately induces COX2 expression and filaggrin downregulation. Up-regulated expression of COX2 and production of PGE2 may lead to impairment of skin barrier function.

UR - http://www.scopus.com/inward/record.url?scp=84975510018&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84975510018&partnerID=8YFLogxK

U2 - 10.1038/srep27995

DO - 10.1038/srep27995

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 27995

ER -