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Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK cell-originated protein kinase.
Oncotarget 2017; 8(16):27093-27104O

Abstract

Excessive exposure to solar UV (SUV) is related with numerous human skin disorders, such as skin inflammation, photoaging and carcinogenesis. T-LAK cell- originated protein kinase (TOPK), an upstream of p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinases (JNKs), plays an important role in SUV -induced skin inflammation, and targeting TOPK has already been a strategy to prevent skin inflammation. In this study, we found that the expression of TOPK, phosphorylation of p38 or JNKs was increased in human solar dermatitis tissues. The level of phosphorylation of p38 or JNKs increased in a dose and time dependent manner in HaCat cells or JB6 Cl41 cells after SUV treatment. Paeonol is an active component isolated from traditional Chinese herbal medicines, and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2H-tetrazdium) assay showed that it has no toxicity to cells. Microscale thermophoresis (MST) assay showed that paeonol can bind TOPK ex vivo. In vitro kinase assay showed paeonol can inhibit TOPK activity. Ex vivo studies further showed paeonol suppressed SUV-induced phosphorylation level of p38, JNKs, MSK1 and histone H2AX by inhibiting TOPK activity in a time and dose dependent manner. Paeonol inhibited the secretion of IL-6 and TNF-α in HaCat and JB6 cells ex vivo. In vivo studies demonstrated that paeonol inhibited SUV-induced increase of TOPK, the phosphorylation of p38, JNKs and H2AX, and the secretion of IL-6 and TNF-α in Babl/c mouse. In summary, our data indicated a protective role of paeonol against SUV-induced inflammation by targeting TOPK, and paeonol could be a promising agent for the treatment of SUV-induced skin inflammation.

Authors+Show Affiliations

Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Dermatology of The General Hospital of Air Force, Beijing, 100142, PR China.Department of Dermatology of The General Hospital of Air Force, Beijing, 100142, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Pathology, Union Hospital, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Dermatology of The General Hospital of Air Force, Beijing, 100142, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.Department of Dermatology of The General Hospital of Air Force, Beijing, 100142, PR China.Department of Biochemistry and Molecular Biology, School of Basic Medicine, Huazhong University of Science and Technology, Wuhan, 430030, China.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28404919

Citation

Xue, Peipei, et al. "Paeonol Suppresses Solar Ultraviolet-induced Skin Inflammation By Targeting T-LAK Cell-originated Protein Kinase." Oncotarget, vol. 8, no. 16, 2017, pp. 27093-27104.
Xue P, Wang Y, Zeng F, et al. Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK cell-originated protein kinase. Oncotarget. 2017;8(16):27093-27104.
Xue, P., Wang, Y., Zeng, F., Xiu, R., Chen, J., Guo, J., ... Duan, Q. (2017). Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK cell-originated protein kinase. Oncotarget, 8(16), pp. 27093-27104. doi:10.18632/oncotarget.15636.
Xue P, et al. Paeonol Suppresses Solar Ultraviolet-induced Skin Inflammation By Targeting T-LAK Cell-originated Protein Kinase. Oncotarget. 2017 Apr 18;8(16):27093-27104. PubMed PMID: 28404919.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Paeonol suppresses solar ultraviolet-induced skin inflammation by targeting T-LAK cell-originated protein kinase. AU - Xue,Peipei, AU - Wang,Yong, AU - Zeng,Fanfan, AU - Xiu,Ruijuan, AU - Chen,Jingwen, AU - Guo,Jinguang, AU - Yuan,Ping, AU - Liu,Lin, AU - Xiao,Juanjuan, AU - Lu,Hui, AU - Wu,Dan, AU - Pan,Huaxiong, AU - Lu,Mingmin, AU - Zhu,Feng, AU - Shi,Fei, AU - Duan,Qiuhong, PY - 2016/11/24/received PY - 2017/01/24/accepted PY - 2017/4/14/pubmed PY - 2018/3/6/medline PY - 2017/4/14/entrez KW - MAPK KW - TOPK KW - paeonol KW - skin inflammation KW - solar UV SP - 27093 EP - 27104 JF - Oncotarget JO - Oncotarget VL - 8 IS - 16 N2 - Excessive exposure to solar UV (SUV) is related with numerous human skin disorders, such as skin inflammation, photoaging and carcinogenesis. T-LAK cell- originated protein kinase (TOPK), an upstream of p38 mitogen-activated protein kinase (p38) and c-Jun N-terminal kinases (JNKs), plays an important role in SUV -induced skin inflammation, and targeting TOPK has already been a strategy to prevent skin inflammation. In this study, we found that the expression of TOPK, phosphorylation of p38 or JNKs was increased in human solar dermatitis tissues. The level of phosphorylation of p38 or JNKs increased in a dose and time dependent manner in HaCat cells or JB6 Cl41 cells after SUV treatment. Paeonol is an active component isolated from traditional Chinese herbal medicines, and MTS (3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2H-tetrazdium) assay showed that it has no toxicity to cells. Microscale thermophoresis (MST) assay showed that paeonol can bind TOPK ex vivo. In vitro kinase assay showed paeonol can inhibit TOPK activity. Ex vivo studies further showed paeonol suppressed SUV-induced phosphorylation level of p38, JNKs, MSK1 and histone H2AX by inhibiting TOPK activity in a time and dose dependent manner. Paeonol inhibited the secretion of IL-6 and TNF-α in HaCat and JB6 cells ex vivo. In vivo studies demonstrated that paeonol inhibited SUV-induced increase of TOPK, the phosphorylation of p38, JNKs and H2AX, and the secretion of IL-6 and TNF-α in Babl/c mouse. In summary, our data indicated a protective role of paeonol against SUV-induced inflammation by targeting TOPK, and paeonol could be a promising agent for the treatment of SUV-induced skin inflammation. SN - 1949-2553 UR - https://www.unboundmedicine.com/medline/citation/28404919/Paeonol_suppresses_solar_ultraviolet_induced_skin_inflammation_by_targeting_T_LAK_cell_originated_protein_kinase_ L2 - http://www.impactjournals.com/oncotarget/misc/linkedout.php?pii=15636 DB - PRIME DP - Unbound Medicine ER -