Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation
UVB skin pathology is initiated by reactive oxygen species (ROS), differentiating this condition from other inflammatory diseases involving first the immune cell activation by danger or pathogen molecular patterns followed by oxidative stress. Resolvin D2 (RvD2) has been found to reduce inflammation...
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MDPI AG
2025-07-01
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| author | Ingrid C. Pinto Priscila Saito Camilla C. A. Rodrigues Renata M. Martinez Cristina P. B. Melo Maiara Piva Clovis M. Kumagai David L. Vale Telma Saraiva-Santos Allan J. C. Bussmann Marcela M. Baracat Sandra R. Georgetti Fabiana T. M. C. Vicentini Waldiceu A. Verri Rubia Casagrande |
| author_facet | Ingrid C. Pinto Priscila Saito Camilla C. A. Rodrigues Renata M. Martinez Cristina P. B. Melo Maiara Piva Clovis M. Kumagai David L. Vale Telma Saraiva-Santos Allan J. C. Bussmann Marcela M. Baracat Sandra R. Georgetti Fabiana T. M. C. Vicentini Waldiceu A. Verri Rubia Casagrande |
| author_sort | Ingrid C. Pinto |
| collection | DOAJ |
| description | UVB skin pathology is initiated by reactive oxygen species (ROS), differentiating this condition from other inflammatory diseases involving first the immune cell activation by danger or pathogen molecular patterns followed by oxidative stress. Resolvin D2 (RvD2) has been found to reduce inflammation in preclinical models. However, whether or not RvD2 reduces skin pathology caused by UVB irradiation is not yet known. Therefore, the efficacy of RvD2 on skin pathology triggered by UVB irradiation in female hairless mice was assessed. RvD2 (0.3, 1 or 3 ng/mouse, i.p.) was found to protect the skin against UVB inflammation, as observed in the reduction in edema (46%), myeloperoxidase activity (77%), metalloproteinase-9 activity (39%), recruitment of neutrophils/macrophages (lysozyme<sup>+</sup> cells, 76%) and mast cells (106%), epidermal thickening (93%), sunburn cell formation (68%), collagen fiber breakdown (55%), and production of cytokines such as TNF-α (100%). Considering the relevance of oxidative stress to UVB irradiation skin pathologies, an important observation was that the skin antioxidant capacity was recovered by RvD2 according to the results that show the ferric reducing antioxidant power (68%), cationic radical scavenges (93%), catalase activity (74%), and the levels of reduced glutathione (48%). Oxidative damage was also attenuated, as observed in the reduction in superoxide anion production (69%) and lipid hydroperoxides (71%). The RvD2 mechanism involved the inhibition of NF-κB activation, as observed in the diminished degradation of IκBα (48%) coupled with a reduction in its downstream targets that are involved in inflammation and oxidative stress, such as COX-2 (66%) and gp91<sup>phox</sup> (77%) mRNA expression. In conclusion, RvD2 mitigates the inflammatory and oxidative pathologic skin aggression that is triggered by UVB. |
| format | Article |
| id | doaj-art-ef161a6cfd1f4bb89e67ad31c8da8748 |
| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Antioxidants |
| spelling | doaj-art-ef161a6cfd1f4bb89e67ad31c8da87482025-08-20T03:13:39ZengMDPI AGAntioxidants2076-39212025-07-0114783010.3390/antiox14070830Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB ActivationIngrid C. Pinto0Priscila Saito1Camilla C. A. Rodrigues2Renata M. Martinez3Cristina P. B. Melo4Maiara Piva5Clovis M. Kumagai6David L. Vale7Telma Saraiva-Santos8Allan J. C. Bussmann9Marcela M. Baracat10Sandra R. Georgetti11Fabiana T. M. C. Vicentini12Waldiceu A. Verri13Rubia Casagrande14Department of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilDepartment of Immunology, Parasitology and General Pathology, Centre of Biological Sciences, Londrina State University, Rodovia Celso Garcia Cid, Km 380, PR445, Cx. Postal 10.011, Londrina 86057-970, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilDepartment of Immunology, Parasitology and General Pathology, Centre of Biological Sciences, Londrina State University, Rodovia Celso Garcia Cid, Km 380, PR445, Cx. Postal 10.011, Londrina 86057-970, PR, BrazilDepartment of Immunology, Parasitology and General Pathology, Centre of Biological Sciences, Londrina State University, Rodovia Celso Garcia Cid, Km 380, PR445, Cx. Postal 10.011, Londrina 86057-970, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilSchool of Pharmaceutical Sciences of Ribeirão Preto, University of São Paulo, Av. Café, Ribeirão Preto 14048-900, SP, BrazilDepartment of Immunology, Parasitology and General Pathology, Centre of Biological Sciences, Londrina State University, Rodovia Celso Garcia Cid, Km 380, PR445, Cx. Postal 10.011, Londrina 86057-970, PR, BrazilDepartment of Pharmaceutical Sciences, Centre of Health Science, Londrina State University, Avenida Robert Koch, 60, Londrina 86038-350, PR, BrazilUVB skin pathology is initiated by reactive oxygen species (ROS), differentiating this condition from other inflammatory diseases involving first the immune cell activation by danger or pathogen molecular patterns followed by oxidative stress. Resolvin D2 (RvD2) has been found to reduce inflammation in preclinical models. However, whether or not RvD2 reduces skin pathology caused by UVB irradiation is not yet known. Therefore, the efficacy of RvD2 on skin pathology triggered by UVB irradiation in female hairless mice was assessed. RvD2 (0.3, 1 or 3 ng/mouse, i.p.) was found to protect the skin against UVB inflammation, as observed in the reduction in edema (46%), myeloperoxidase activity (77%), metalloproteinase-9 activity (39%), recruitment of neutrophils/macrophages (lysozyme<sup>+</sup> cells, 76%) and mast cells (106%), epidermal thickening (93%), sunburn cell formation (68%), collagen fiber breakdown (55%), and production of cytokines such as TNF-α (100%). Considering the relevance of oxidative stress to UVB irradiation skin pathologies, an important observation was that the skin antioxidant capacity was recovered by RvD2 according to the results that show the ferric reducing antioxidant power (68%), cationic radical scavenges (93%), catalase activity (74%), and the levels of reduced glutathione (48%). Oxidative damage was also attenuated, as observed in the reduction in superoxide anion production (69%) and lipid hydroperoxides (71%). The RvD2 mechanism involved the inhibition of NF-κB activation, as observed in the diminished degradation of IκBα (48%) coupled with a reduction in its downstream targets that are involved in inflammation and oxidative stress, such as COX-2 (66%) and gp91<sup>phox</sup> (77%) mRNA expression. In conclusion, RvD2 mitigates the inflammatory and oxidative pathologic skin aggression that is triggered by UVB.https://www.mdpi.com/2076-3921/14/7/830pro-resolution lipidantioxidantUV radiationinflammation |
| spellingShingle | Ingrid C. Pinto Priscila Saito Camilla C. A. Rodrigues Renata M. Martinez Cristina P. B. Melo Maiara Piva Clovis M. Kumagai David L. Vale Telma Saraiva-Santos Allan J. C. Bussmann Marcela M. Baracat Sandra R. Georgetti Fabiana T. M. C. Vicentini Waldiceu A. Verri Rubia Casagrande Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation Antioxidants pro-resolution lipid antioxidant UV radiation inflammation |
| title | Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation |
| title_full | Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation |
| title_fullStr | Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation |
| title_full_unstemmed | Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation |
| title_short | Resolvin D2 Reduces UVB Skin Pathology by Targeting Cytokines, Oxidative Stress, and NF-κB Activation |
| title_sort | resolvin d2 reduces uvb skin pathology by targeting cytokines oxidative stress and nf κb activation |
| topic | pro-resolution lipid antioxidant UV radiation inflammation |
| url | https://www.mdpi.com/2076-3921/14/7/830 |
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