title: Photoprotective Potential of Glycolic Acid by Reducing NLRC4 and AIM2 Inflammasome Complex Proteins in UVB Radiation-Induced Normal Human Epidermal Keratinocytes and Mice.
abstract: Exposure to UVB radiation induces inflammation and free radical-mediated oxidative stress through reactive oxygen species (ROS) that play a crucial role in the induction of skin cancer. Glycolic acid (GA) is frequently used in cosmetics and dermatology. The aim of the study was to analyze the photoprotective mechanisms through which GA retards UVB-induced ROS accumulation and inflammation in normal human epidermal keratinocytes (NHEKs) and mice skin, respectively. NHEK cell line and C57BL/6J mice were treated with GA (0.1 or 5 mM) for 24 h followed by UVB irradiation. ROS accumulation, DNA damage, and expression of inflammasome complexes (NLRP3, NLRC4, ASC, and AIM2) were measured in vitro. Epidermal thickness and inflammasome complex proteins were analyzed in vivo. GA significantly prevented UVB-induced loss of skin cell viability, ROS formation, and DNA damage (single and double strands DNA break). GA suppressed the mRNA expression levels of NLRC4 and AIM2 among the inflammasome complexes. GA also blocked interleukin (IL)-1β by reducing the activity of caspase-1 in the NHEKs. Treatment with GA (2%) inhibited UVB-induced inflammation marker NLRC4 protein levels in mouse dorsal skin. The photoprotective activity of GA was ascribed to the inhibition of ROS formation and DNA damage, as well as a reduction in the activities of inflammasome complexes and IL-1β. We propose that GA has anti-inflammatory and photoprotective effects against UVB irradiation. GA is potentially beneficial to the protection of human skin from UV damage.
authors.affiliation: 1 Department of Dermatology, Buddhist Tzu Chi General Hospital , Hualien, Taiwan .|2 Institute of Medical Sciences, Tzu Chi University , Hualien, Taiwan .
authors.forename: Sung-Jen
authors.initials: SJ
authors.lastname: Hung
authors.affiliation: 2 Institute of Medical Sciences, Tzu Chi University , Hualien, Taiwan .|3 Department of Biochemistry, School of Medicine, Tzu Chi University , Hualien, Taiwan .|4 Institute of Biomedical Sciences , Academia Sinica, Taipei, Taiwan .
authors.forename: Sheau-Chung
authors.initials: SC
authors.lastname: Tang
authors.affiliation: 1 Department of Dermatology, Buddhist Tzu Chi General Hospital , Hualien, Taiwan .|2 Institute of Medical Sciences, Tzu Chi University , Hualien, Taiwan .
authors.forename: Pei-Yun
authors.initials: PY
authors.lastname: Liao
authors.affiliation: 1 Department of Dermatology, Buddhist Tzu Chi General Hospital , Hualien, Taiwan .
authors.forename: Jheng-Siang
authors.initials: JS
authors.lastname: Ge
authors.affiliation: 5 Institute of Medicine, School of Medicine, Chung Shan Medical University , Taichung, Taiwan .|6 Department of Dermatology, Chung Shan Medical University Hospital , Taichung, Taiwan .
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Hsiao
authors.affiliation: 1 Department of Dermatology, Buddhist Tzu Chi General Hospital , Hualien, Taiwan .|3 Department of Biochemistry, School of Medicine, Tzu Chi University , Hualien, Taiwan .|7 Institute of Medicine, School of Medicine, Tzu Chi University , Hualien, Taiwan .
authors.forename: Jen-Hung
authors.initials: JH
authors.lastname: Yang
mesh_terms: D000818:Animals; D053468:CARD Signaling Adaptor Proteins / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D020170:Caspase 1 / Q000235:genetics; D053938:DNA Fragmentation / Q000187:drug effects / Q000528:radiation effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000078404:Epidermal Cells; D005786:Gene Expression Regulation / Q000187:drug effects / Q000528:radiation effects; D006016:Glycolates / Q000494:pharmacology*; D006657:Histones / Q000378:metabolism; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D053583:Interleukin-1beta / Q000096:biosynthesis / Q000378:metabolism; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D051379:Mice; D008810:Mice, Inbred C57BL; D011837:Radiation-Protective Agents / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: C410167:AIM2 protein, human; D053468:CARD Signaling Adaptor Proteins; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D006016:Glycolates; C468783:H2AX protein, human; D006657:Histones; D058847:Inflammasomes; D053583:Interleukin-1beta; C435692:NLRC4 protein, human; D011837:Radiation-Protective Agents; D017382:Reactive Oxygen Species; C031149:glycolic acid; D020170:Caspase 1
keywords: glycolic acid–alpha-hydroxy acids; inflammasome complexes–NLRC4; normal human epidermal keratinocytes; reactive oxygen species