Topical application of glycolic acid suppresses the UVB induced IL-6, IL-8, MCP-1 and COX-2 inflammation by modulating NF-κB signaling pathway in keratinocytes and mice skin.
BACKGROUND
Glycolic acid (GA), commonly present in fruits, has been used to treat dermatological diseases. Extensive exposure to solar ultraviolet B (UVB) irradiation plays a crucial role in the induction of skin inflammation. The development of photo prevention from natural materials represents an effective strategy for skin keratinocytes.


OBJECTIVE
The aim of this study was to investigate the molecular mechanisms underlying the glycolic acid (GA)-induced reduction of UVB-mediated inflammatory responses.


METHODS
We determined the effects of different concentrations of GA on the inflammatory response of human keratinocytes HaCaT cells and C57BL/6J mice dorsal skin. After GA was topically applied, HaCaT and mice skin were exposed to UVB irradiation.


RESULTS
GA reduced the production of UVB-induced nuclear factor kappa B (NF-κB)-dependent inflammatory mediators [interleukin (IL)-1β, IL-6, IL-8, cyclooxygenase (COX)-2, tumor necrosis factor-α, and monocyte chemoattractant protein (MCP-1)] at both mRNA and protein levels. GA inhibited the UVB-induced promoter activity of NF-κB in HaCaT cells. GA attenuated the elevation of senescence associated with β-galactosidase activity but did not affect the wound migration ability. The topical application of GA inhibited the genes expression of IL-1β, IL-6, IL-8, COX-2, and MCP-1 in UVB-exposed mouse skin. The mice to UVB irradiation after GA was topically applied for 9 consecutive days and reported that 1-1.5% of GA exerted anti-inflammatory effects on mouse skin.


CONCLUSIONS
We clarified the molecular mechanism of GA protection against UVB-induced inflammation by modulating NF-κB signaling pathways and determined the optimal concentration of GA in mice skin exposed to UVB irradiation.
Department of Dermatology, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan; Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan.
Sheau-Chung
SC
Tang
Department of Dermatology, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan; Institute of Medical Sciences, Tzu Chi University, Hualien 97004, Taiwan.
Pei-Yun
PY
Liao
Department of Dermatology, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan.
Sung-Jen
SJ
Hung
Department of Dermatology, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan.
Jheng-Siang
JS
Ge
Department of Dermatology, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan.
Shiou-Mei
SM
Chen
Research Assistant Center, Chang Hua Show Chwan Health, Care System, Changhua 50008, Taiwan.
Ji-Ching
JC
Lai
Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung 40244, Taiwan; Department of Dermatology, Chung Shan Medical University Hospital, Taichung 40244, Taiwan.
Yu-Ping
YP
Hsiao
Department of Dermatology, Buddhist Tzu Chi General Hospital, Hualien 97004, Taiwan; Department of Biochemistry, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan; Institute of Medicine, School of Medicine, Tzu Chi University, Hualien 97004, Taiwan. Electronic address: jh.med.edu@gms.tcu.edu.tw.
Jen-Hung
JH
Yang
D000279:Administration, Cutaneous; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects / Q000528:radiation effects; D016922:Cellular Senescence / Q000187:drug effects / Q000528:radiation effects; D018932:Chemokine CCL2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006016:Glycolates / Q000008:administration & dosage*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D016209:Interleukin-8 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects*; D008297:Male; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000528:radiation effects; D012867:Skin / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology / Q000528:radiation effects*; D013997:Time Factors; D014162:Transfection; D014466:Ultraviolet Rays
D000893:Anti-Inflammatory Agents; C111835:CCL2 protein, human; C508606:CXCL8 protein, human; C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D006016:Glycolates; C508600:IL6 protein, human; D015850:Interleukin-6; D016209:Interleukin-8; D016328:NF-kappa B; D012333:RNA, Messenger; C577686:interleukin-6, mouse; C031149:glycolic acid; C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
Glycolic acid (GA); cyclooxygenase (COX)-2; interleukin (IL)-1β; monocyte chemoattractant protein (MCP-1); nuclear factor kappa B (NF-κB); ultraviolet B (UVB)