Curcumin Improves Keratinocyte Proliferation, Inflammation, and Oxidative Stress through Mediating the SPAG5/FOXM1 Axis in an In Vitro Model of Actinic Dermatitis by Ultraviolet.

Abstract

Background:

Chronic actinic dermatitis (CAD) is an abnormally proliferating photoallergic skin disease. Dysregulated inflammation and oxidative stress are the immediate factors in the abnormal proliferation of keratinocytes. This study aimed to investigate the effect of curcumin on the aberrant proliferation of keratinocytes in an in vitro (actinic dermatitis) AD model and the possible molecular mechanisms.

Methods:

The keratinocytes were irradiated with ultraviolet (UV) to construct an in vitro AD model and then processed with different concentrations of curcumin. Cell viability, oxidative stress markers (SOD, GSH-PX, and MDA), activated oxygen species (ROS), and inflammation markers (IL-1β, IL-6, IL-18, and TNFα) were determined, respectively. Western blot was applied to assay the profiles of apoptosis-related proteins (Bax, Bcl-xL, Caspase3, Caspase8, and Caspase9), oxidative stress proteins (Keap1, Nrf2, HO-1, COX2, and iNOS), and inflammatory proteins (NF-κB, MMP1, and MMP9) and SPAG5/FOXM1. Functionally, SPAG5 or FOXM1 overexpression and knockdown models were constructed in keratinocytes to characterize their influence on UV irradiation-mediated keratinocyte dysfunction.

Results:

Curcumin weakened UV-mediated inflammation, proliferation, and oxidative stress and impaired apoptosis in keratinocytes. UV boosted SPAG5/FOXM1 expression in cells, while curcumin concentration-dependently retarded SPAG5/FOXM1 expression. Overexpression of SPAG5/FOXM1 fostered UV-mediated inflammation, proliferation, oxidative stress, and intensified apoptosis, whereas curcumin mostly reversed the SPAG5/FOXM1-mediated effects. In addition, knocking down SPAG5/FOXM1 ameliorated UV-mediated keratinocyte dysfunction, whereas curcumin failed to exert further protective effects in cells with knockdown of SPAG5/FOXM1.

Conclusion:

Curcumin modulated proliferation, inflammation, oxidative stress, and apoptosis of keratinocytes by restraining the SPAG5/FOXM1 axis.

• Authors: Quan Chen, Yi Tang, Huiyan Deng, Bihua Liang, Huaping Li, Zhenjie Li, Huilan Zhu, Lezi Chen
• Journal: Disease markers (Dis Markers) Vol. 2022 Pg. 5085183 ( 2022) ISSN: 1875-8630 [Electronic] United States
• PMID: 36118675 (Publication Type: Journal Article)
• Copyright: Copyright © 2022 Quan Chen et al.

Chemical References

• Cell Cycle Proteins
• FOXM1 protein, human
• Forkhead Box Protein M1
• Interleukin-18
• Interleukin-6
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• NF-kappa B
• Reactive Oxygen Species
• SPAG5 protein, human
• Tumor Necrosis Factor-alpha
• bcl-2-Associated X Protein
• Cyclooxygenase 2
• Superoxide Dismutase
• Matrix Metalloproteinase 9
• Matrix Metalloproteinase 1
• Curcumin
• Oxygen

Topics

• Cell Cycle Proteins
• Cell Proliferation
• Curcumin (metabolism, pharmacology)
• Cyclooxygenase 2 (metabolism, pharmacology)
• Forkhead Box Protein M1
• Humans
• Inflammation (metabolism)
• Interleukin-18 (metabolism)
• Interleukin-6 (metabolism)
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• Keratinocytes (metabolism)
• Matrix Metalloproteinase 1
• Matrix Metalloproteinase 9 (metabolism)
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress
• Oxygen (metabolism, pharmacology)
• Photosensitivity Disorders (metabolism)
• Reactive Oxygen Species (metabolism)
• Superoxide Dismutase (metabolism)
• Tumor Necrosis Factor-alpha (metabolism)
• bcl-2-Associated X Protein (metabolism, pharmacology)