12(S)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid suppresses UV-induced IL-6 synthesis in keratinocytes, exerting an anti-inflammatory activity
- Authors
- Lee, Jin-Wook; Ryu, Ho-Cheol; Ng, Yee Ching; Kim, Cheolmin; Wei, Jun-Dong; Sabaratnam, Vikineswary; Kim, Jae-Hong
- Issue Date
- 30-6월-2012
- Publisher
- KOREAN SOC MED BIOCHEMISTRY MOLECULAR BIOLOGY
- Keywords
- dermatitis; dual specificity phosphatase 1; 12-hydroxy-5,8,10-heptadecatrienoic acid; interleukin-6; ultraviolet rays
- Citation
- EXPERIMENTAL AND MOLECULAR MEDICINE, v.44, no.6, pp.378 - 386
- Indexed
- SCIE
SCOPUS
KCI
- Journal Title
- EXPERIMENTAL AND MOLECULAR MEDICINE
- Volume
- 44
- Number
- 6
- Start Page
- 378
- End Page
- 386
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/108130
- DOI
- 10.3858/emm.2012.44.6.043
- ISSN
- 1226-3613
- Abstract
- 12(5)-Hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is an enzymatic product of prostaglandin H-2 (PGH(2)) 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-kappa B). 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-kappa B, 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-kappa b, 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.
- Files in This Item
- There are no files associated with this item.
- Appears in
Collections - College of Life Sciences and Biotechnology > Division of Life Sciences > 1. Journal Articles
Items in ScholarWorks are protected by copyright, with all rights reserved, unless otherwise indicated.