12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid suppresses UV-induced IL-6 synthesis in keratinocytes, exerting an anti-inflammatory activity

Jin Wook Lee, Ho Cheol Ryu, Yee Ching Ng, Cheolmin Kim, Jun Dong Wei, Vikineswary Sabaratnam, Jae-Hong Kim

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an enzymatic product of prostaglandin H2 (PGH2) derived from cyclooxygenase (COX)-mediated arachidonic acid metabolism. Despite the high level of 12-HHT present in tissues and bodily fluids, its precise function remains largely unknown. In this study, we found that 12-HHT treatment in HaCaT cells remarkably down-regulated the ultraviolet B (UVB) irradiation-induced synthesis of interleukin-6 (IL-6), a pro-inflammatory cytokine associated with cutaneous inflammation. In an approach to identify the down-stream signaling mechanism by which 12-HHT down-regulates UVB-induced IL-6 synthesis in keratinocytes, we observed that 12-HHT inhibits the UVB-stimulated activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB). In addition, we found that 12-HHT markedly up-regulates MAPK phosphatase-1 (MKP-1), a critical negative regulator of p38 MAPK. When MKP-1 was suppressed by siRNA knock-down, the 12-HHT-mediated inhibitory effects on the UVB-stimulated activation of p38 MAPK and NF-κB, as well as the production of IL-6, were attenuated in HaCaT cells. Taken together, our results suggest that 12-HHT exerts anti-inflammatory effect via up-regulation of MKP-1, which negatively regulates p38 MAPK and NF-κB, thus attenuating IL-6 production in UVB-irradiated HaCaT cells. Considering the critical role of IL-6 in cutaneous inflammation, our findings provide the basis for the application of 12-HHT as a potential anti-inflammatory therapeutic agent in UV-induced skin diseases.

Original languageEnglish
Pages (from-to)378-386
Number of pages9
JournalExperimental and Molecular Medicine
Volume44
Issue number6
DOIs
Publication statusPublished - 2012 Jun 1

Fingerprint

Keratinocytes
Interleukin-6
Anti-Inflammatory Agents
Acids
Dual Specificity Phosphatase 1
p38 Mitogen-Activated Protein Kinases
NF-kappa B
Up-Regulation
Mitogen-Activated Protein Kinase Phosphatases
Chemical activation
Prostaglandin H2
Inflammation
12-hydroxy-5,8,10-heptadecatrienoic acid
Skin
Prostaglandin-Endoperoxide Synthases
Skin Diseases
Metabolism
Small Interfering RNA
Down-Regulation
Irradiation

Keywords

  • 12-hydroxy-5,8,10-heptadecatrienoic acid
  • Dermatitis
  • Dual specificity phosphatase 1
  • Interleukin-6
  • Ultraviolet rays

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Molecular Medicine
  • Clinical Biochemistry

Cite this

12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid suppresses UV-induced IL-6 synthesis in keratinocytes, exerting an anti-inflammatory activity. / Lee, Jin Wook; Ryu, Ho Cheol; Ng, Yee Ching; Kim, Cheolmin; Wei, Jun Dong; Sabaratnam, Vikineswary; Kim, Jae-Hong.

In: Experimental and Molecular Medicine, Vol. 44, No. 6, 01.06.2012, p. 378-386.

Research output: Contribution to journalArticle

Lee, Jin Wook ; Ryu, Ho Cheol ; Ng, Yee Ching ; Kim, Cheolmin ; Wei, Jun Dong ; Sabaratnam, Vikineswary ; Kim, Jae-Hong. / 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid suppresses UV-induced IL-6 synthesis in keratinocytes, exerting an anti-inflammatory activity. In: Experimental and Molecular Medicine. 2012 ; Vol. 44, No. 6. pp. 378-386.
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abstract = "12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an enzymatic product of prostaglandin H2 (PGH2) derived from cyclooxygenase (COX)-mediated arachidonic acid metabolism. Despite the high level of 12-HHT present in tissues and bodily fluids, its precise function remains largely unknown. In this study, we found that 12-HHT treatment in HaCaT cells remarkably down-regulated the ultraviolet B (UVB) irradiation-induced synthesis of interleukin-6 (IL-6), a pro-inflammatory cytokine associated with cutaneous inflammation. In an approach to identify the down-stream signaling mechanism by which 12-HHT down-regulates UVB-induced IL-6 synthesis in keratinocytes, we observed that 12-HHT inhibits the UVB-stimulated activation of p38 mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB). In addition, we found that 12-HHT markedly up-regulates MAPK phosphatase-1 (MKP-1), a critical negative regulator of p38 MAPK. When MKP-1 was suppressed by siRNA knock-down, the 12-HHT-mediated inhibitory effects on the UVB-stimulated activation of p38 MAPK and NF-κB, as well as the production of IL-6, were attenuated in HaCaT cells. Taken together, our results suggest that 12-HHT exerts anti-inflammatory effect via up-regulation of MKP-1, which negatively regulates p38 MAPK and NF-κB, thus attenuating IL-6 production in UVB-irradiated HaCaT cells. Considering the critical role of IL-6 in cutaneous inflammation, our findings provide the basis for the application of 12-HHT as a potential anti-inflammatory therapeutic agent in UV-induced skin diseases.",
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AU - Ng, Yee Ching

AU - Kim, Cheolmin

AU - Wei, Jun Dong

AU - Sabaratnam, Vikineswary

AU - Kim, Jae-Hong

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