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.

Cardiac transcriptomic changes induced by early CKD in mice reveal novel pathways involved in the pathogenesis of Cardiorenal syndrome type 4

“…In this transcriptomic study, we describe an abundance of changes occurring in the heart after UUO that comprise a broad spectrum of biological processes. Among them, we identified other UUO-upregulated cardiac genes ( Birc5, Cd300E, Foxm1, Spag5, Hmmr, Dach1, Akap5, and Yes1 ) that could advance our understanding of the relationship between kidney disease and cardiac dysfunction due to their involvement in immune responses, cardiac repair, fibrosis, inflammation, proliferation, oxidative stress, and apoptosis [ [30] , [31] , [32] , [33] ]. These genes could provide novel insights into CKD-related cardiac pathways contributing to CRS progression though their direct contribution needs to be validated experimentally.…”

Deciphering the sequential changes of monocytes/macrophages in the progression of IDD with longitudinal approach using single-cell transcriptome

“…This is the first time that the essential roles of CYPs family with oxidative stress and immune responses were connected with the pathological process of IDD, which were worth of subsequent in-depth research. Existed studies have reported the essential roles of MMPs family and their inhibitors screening in the progression of IDD, among which MMP1 may participate partially through OS-related functions and inflammatory reactions ( 61 , 62 ). NQO1 served as antioxidant genes and played essential roles in ameliorating inflammatory responses, reticulum stress, and apoptosis of degenerative NP cells, which were partially regulated by the antioxidant transcription factor Nrf2 ( 14 , 63 ).…”

Successful Treatment of Chronic Actinic Dermatitis with Tofacitinib

“…Photodermatoses, also known as disorders of cutaneous photosensitivity, encompass a diverse array of inflammatory skin conditions that are triggered or exacerbated by exposure to solar radiation. 1 , 2 Among these, chronic actinic dermatitis (CAD) is a rare, persistent immunological photodermatosis that manifests as a pruritic eczematous eruption on sun-exposed skin when subjected to ultraviolet (UV) light, 3 , 4 encompassing both ultraviolet A and ultraviolet B, as well as visible light, 5 accompanied by the development of papules and lichenified plaques. 6 In severe cases, it can progress to erythroderma with palmoplantar hyperkeratosis, 7 and in some instances, it can transform into cutaneous lymphoma.…”

“… 10 Currently, no curative treatment for CAD. 5 Topical calcineurin inhibitors (TCIs) and topical and systemic corticosteroids are first-line pharmacological management options. In severe cases, indicated systemic immunosuppression usually involves cyclosporine, methotrexate, mycophenolate mofetil, and azathioprine.…”

“…The results demonstrated decreased keratinocyte proliferation, and lower levels of inflammation, oxidative stress, and apoptosis. 5 CAD has also been associated with other pathologies. For instance, individuals with contact allergy to plants, compounds such as sesquiterpene lactones, fragrances, sunscreens components, or those presenting with other types of photodermatoses have a higher risk of developing CAD.…”