Cyto/chemokine profile of in vitro scratched keratinocyte model

Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon

Kazuhisa Furue, Takamichi Ito, Yuka Tanaka, Ayako Yumine, Akiko Hashimoto-Hachiya, Masaki Takemura, Maho Murata, Kazuhiko Yamamura, Gaku Tsuji, Masutaka Furue

Research output: Contribution to journalArticle

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Abstract

Background: Scratch injury induces Koebner phenomenon in psoriasis. Smoking is also a risk factor for psoriasis. Keratinocytes can produce various psoriasis-related molecules including TNF, IL1 A, IL1B, IL6, IL12B, IL17C, IL23 A, IL36 A, IL36B, IL36 G, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10, CCL20, IFNB, and CAMP. However, the scratch-induced molecular profiling remains elusive. Objective: To profile the induction pattern of above-mentioned psoriasis-related and keratinocyte-derived molecules by scratch injury in the presence or absence of anti-psoriatic drugs or benzo[a]pyrene, a major environmental pollutant of tobacco smoke. Methods: Confluent normal human keratinocytes were scratched and molecules were assayed by qRT-PCR, ELISA and Western blotting with or without drugs and benzo[a]pyrene. Results: Among the 18 molecules, the scratch injury on a confluent keratinocyte sheet significantly and selectively upregulated the mRNA expression of four cyto/chemokines, CXCL8, CCL20, IL36G, and TNF, in a scratch-line-number-dependent manner under either low- or high-calcium condition. However, significant protein secretion was only demonstrated for CXCL8 and CCL20. The IL36 G protein was not secreted, but its intracellular level was significantly upregulated by scratch injury, whereas neither the secretion nor the intracellular level of TNF protein was affected by scratch injury. Dexamethasone, but not maxacalcitol nor the phosphodiesterase 4 inhibitor apremilast, partially inhibited the CXCL8 and CCL20 secretion. Benzo[a]pyrene significantly and synergistically enhanced the scratch-induced CCL20 secretion that may explain why smoking is a risk factor for psoriasis. Conclusion: CCL20 and to a less extent CXCL8 may play a key role in triggering the Koebner phenomenon after scratch injury to keratinocytes.

Original languageEnglish
Pages (from-to)244-251
Number of pages8
JournalJournal of Dermatological Science
Volume94
Issue number1
DOIs
Publication statusPublished - Apr 1 2019

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Keratinocytes
Chemokines
Psoriasis
Up-Regulation
Benzo(a)pyrene
Wounds and Injuries
Molecules
Chemokine CCL20
Phosphodiesterase 4 Inhibitors
Calcium
Smoking
Environmental Pollutants
Tobacco
Interleukin-8
GTP-Binding Proteins
Smoke
Pharmaceutical Preparations
Dexamethasone
Interleukin-6
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Dermatology

Cite this

Cyto/chemokine profile of in vitro scratched keratinocyte model : Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon. / Furue, Kazuhisa; Ito, Takamichi; Tanaka, Yuka; Yumine, Ayako; Hashimoto-Hachiya, Akiko; Takemura, Masaki; Murata, Maho; Yamamura, Kazuhiko; Tsuji, Gaku; Furue, Masutaka.

In: Journal of Dermatological Science, Vol. 94, No. 1, 01.04.2019, p. 244-251.

Research output: Contribution to journalArticle

Furue, Kazuhisa ; Ito, Takamichi ; Tanaka, Yuka ; Yumine, Ayako ; Hashimoto-Hachiya, Akiko ; Takemura, Masaki ; Murata, Maho ; Yamamura, Kazuhiko ; Tsuji, Gaku ; Furue, Masutaka. / Cyto/chemokine profile of in vitro scratched keratinocyte model : Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon. In: Journal of Dermatological Science. 2019 ; Vol. 94, No. 1. pp. 244-251.
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title = "Cyto/chemokine profile of in vitro scratched keratinocyte model: Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon",
abstract = "Background: Scratch injury induces Koebner phenomenon in psoriasis. Smoking is also a risk factor for psoriasis. Keratinocytes can produce various psoriasis-related molecules including TNF, IL1 A, IL1B, IL6, IL12B, IL17C, IL23 A, IL36 A, IL36B, IL36 G, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10, CCL20, IFNB, and CAMP. However, the scratch-induced molecular profiling remains elusive. Objective: To profile the induction pattern of above-mentioned psoriasis-related and keratinocyte-derived molecules by scratch injury in the presence or absence of anti-psoriatic drugs or benzo[a]pyrene, a major environmental pollutant of tobacco smoke. Methods: Confluent normal human keratinocytes were scratched and molecules were assayed by qRT-PCR, ELISA and Western blotting with or without drugs and benzo[a]pyrene. Results: Among the 18 molecules, the scratch injury on a confluent keratinocyte sheet significantly and selectively upregulated the mRNA expression of four cyto/chemokines, CXCL8, CCL20, IL36G, and TNF, in a scratch-line-number-dependent manner under either low- or high-calcium condition. However, significant protein secretion was only demonstrated for CXCL8 and CCL20. The IL36 G protein was not secreted, but its intracellular level was significantly upregulated by scratch injury, whereas neither the secretion nor the intracellular level of TNF protein was affected by scratch injury. Dexamethasone, but not maxacalcitol nor the phosphodiesterase 4 inhibitor apremilast, partially inhibited the CXCL8 and CCL20 secretion. Benzo[a]pyrene significantly and synergistically enhanced the scratch-induced CCL20 secretion that may explain why smoking is a risk factor for psoriasis. Conclusion: CCL20 and to a less extent CXCL8 may play a key role in triggering the Koebner phenomenon after scratch injury to keratinocytes.",
author = "Kazuhisa Furue and Takamichi Ito and Yuka Tanaka and Ayako Yumine and Akiko Hashimoto-Hachiya and Masaki Takemura and Maho Murata and Kazuhiko Yamamura and Gaku Tsuji and Masutaka Furue",
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T1 - Cyto/chemokine profile of in vitro scratched keratinocyte model

T2 - Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon

AU - Furue, Kazuhisa

AU - Ito, Takamichi

AU - Tanaka, Yuka

AU - Yumine, Ayako

AU - Hashimoto-Hachiya, Akiko

AU - Takemura, Masaki

AU - Murata, Maho

AU - Yamamura, Kazuhiko

AU - Tsuji, Gaku

AU - Furue, Masutaka

PY - 2019/4/1

Y1 - 2019/4/1

N2 - Background: Scratch injury induces Koebner phenomenon in psoriasis. Smoking is also a risk factor for psoriasis. Keratinocytes can produce various psoriasis-related molecules including TNF, IL1 A, IL1B, IL6, IL12B, IL17C, IL23 A, IL36 A, IL36B, IL36 G, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10, CCL20, IFNB, and CAMP. However, the scratch-induced molecular profiling remains elusive. Objective: To profile the induction pattern of above-mentioned psoriasis-related and keratinocyte-derived molecules by scratch injury in the presence or absence of anti-psoriatic drugs or benzo[a]pyrene, a major environmental pollutant of tobacco smoke. Methods: Confluent normal human keratinocytes were scratched and molecules were assayed by qRT-PCR, ELISA and Western blotting with or without drugs and benzo[a]pyrene. Results: Among the 18 molecules, the scratch injury on a confluent keratinocyte sheet significantly and selectively upregulated the mRNA expression of four cyto/chemokines, CXCL8, CCL20, IL36G, and TNF, in a scratch-line-number-dependent manner under either low- or high-calcium condition. However, significant protein secretion was only demonstrated for CXCL8 and CCL20. The IL36 G protein was not secreted, but its intracellular level was significantly upregulated by scratch injury, whereas neither the secretion nor the intracellular level of TNF protein was affected by scratch injury. Dexamethasone, but not maxacalcitol nor the phosphodiesterase 4 inhibitor apremilast, partially inhibited the CXCL8 and CCL20 secretion. Benzo[a]pyrene significantly and synergistically enhanced the scratch-induced CCL20 secretion that may explain why smoking is a risk factor for psoriasis. Conclusion: CCL20 and to a less extent CXCL8 may play a key role in triggering the Koebner phenomenon after scratch injury to keratinocytes.

AB - Background: Scratch injury induces Koebner phenomenon in psoriasis. Smoking is also a risk factor for psoriasis. Keratinocytes can produce various psoriasis-related molecules including TNF, IL1 A, IL1B, IL6, IL12B, IL17C, IL23 A, IL36 A, IL36B, IL36 G, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10, CCL20, IFNB, and CAMP. However, the scratch-induced molecular profiling remains elusive. Objective: To profile the induction pattern of above-mentioned psoriasis-related and keratinocyte-derived molecules by scratch injury in the presence or absence of anti-psoriatic drugs or benzo[a]pyrene, a major environmental pollutant of tobacco smoke. Methods: Confluent normal human keratinocytes were scratched and molecules were assayed by qRT-PCR, ELISA and Western blotting with or without drugs and benzo[a]pyrene. Results: Among the 18 molecules, the scratch injury on a confluent keratinocyte sheet significantly and selectively upregulated the mRNA expression of four cyto/chemokines, CXCL8, CCL20, IL36G, and TNF, in a scratch-line-number-dependent manner under either low- or high-calcium condition. However, significant protein secretion was only demonstrated for CXCL8 and CCL20. The IL36 G protein was not secreted, but its intracellular level was significantly upregulated by scratch injury, whereas neither the secretion nor the intracellular level of TNF protein was affected by scratch injury. Dexamethasone, but not maxacalcitol nor the phosphodiesterase 4 inhibitor apremilast, partially inhibited the CXCL8 and CCL20 secretion. Benzo[a]pyrene significantly and synergistically enhanced the scratch-induced CCL20 secretion that may explain why smoking is a risk factor for psoriasis. Conclusion: CCL20 and to a less extent CXCL8 may play a key role in triggering the Koebner phenomenon after scratch injury to keratinocytes.

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