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Role of p38 MAPK in UVB-Induced Inflammatory Responses in the Skin of SKH-1 Hairless Mice
Open accessAbstract
The p38 mitogen-activated protein kinase (MAPK) signaling pathway is activated by numerous inflammatory mediators and environmental stresses. We assessed the effects of ultraviolet B (UVB) on the p38 MAPK pathway and determined whether cyclooxygenase (COX)-2 expression is downstream of this kinase in the skin of UVB-irradiated SKH-1 mice. SKH-1 mice were irradiated with a single dose of UVB (360 mJ per cm2), and activation of the epidermal p38 MAPK pathway was assessed. UVB-induced phosphorylation of p38 MAPK occurred in a time-dependent manner. Phosphorylation of MAPK-activated protein kinase-2 (MAPKAPK-2) also was detected and correlated with an increase in its kinase activity. Phosphorylation of heat shock protein 27 (HSP27), a substrate for MAPKAPK-2, also was detected post-irradiation. Oral administration of the p38 inhibitor, SB242235, prior to UVB irradiation, blocked activation of the p38 MAPK cascade, and abolished MAPKAPK-2 kinase activity and phosphorylation of HSP27. Moreover, SB242235 inhibited expression of the pro-inflammatory cytokines interleukin (IL)-6 and KC (murine IL-8) and COX-2. Our data demonstrate that UVB irradiation of murine skin activates epidermal p38 MAPK signaling and induces a local pro-inflammatory response. Blockade of the p38 MAPK pathway may offer an effective approach to reducing or preventing skin damage resulting from acute solar radiation.
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“UV radiation promotes inflammation through several distinct mechanisms, such as activation of the inflammasome and pro-inflammatory cytokines, as well as major inflammation-related signaling pathways such as NF-κB and p38 ( 34 , 35 )”
From Photorepair of Either CPD or 6-4PP DNA Lesions in Basal Keratinocytes Attenuates Ultraviolet-Induced Skin Effects in Nucleotide Excision Repair Deficient Mice (2022) · cites this paper as [34]
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Metadata
- Authors
- Kim, A. L., Labasi, J. M., Zhu, Y., Tang, X., McClure, K., Gabel, C. A., Athar, M., & Bickers, D. R.
- Affiliations
- Columbia University Irving Medical Center (US)
- Pfizer (United States) (US)
- Columbia University (US)
- Corresponding author
- Kim, Arianna L.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2005-06
- Volume
- 124
- Issue
- 6
- Pages
- 1318-1325
- ISSN
- 0022-202X (ISSN-L)
- OpenAlex
- W1964414267
- Cited by
- 153
- References
- 61
- Citations by year
- 2026: 4 · 2025: 2 · 2024: 12 · 2023: 6 · 2022: 17 · 2021: 10 · 2020: 4 · 2019: 10 · 2018: 8 · 2017: 7 · 2016: 6 · 2015: 6 · 2014: 7 · 2013: 9 · 2012: 8
- FWCI
- 8.89
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (K01AR048582)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Keywords
- p38 MAPK, UV-B radiation, skin inflammation, SKH-1 mice, cyclooxygenase-2, MAPKAPK2, HSP27, interleukin-6, photoprotection
- MeSH terms
- MAP-Kinase-Activated Kinase 2, Animals, Enzyme Inhibitors, Female, Heat-Shock Proteins, Imidazoles, Mice, Hairless, Phosphorylation, Photosensitivity Disorders, Prostaglandin-Endoperoxide Synthases, Pyridines, Skin, Threonine, Ultraviolet Rays, Signal Transduction, Cytokines, Protein Serine-Threonine Kinases, Inflammation Mediators, Intracellular Signaling Peptides and Proteins, p38 Mitogen-Activated Protein Kinases, Mice, Cyclooxygenase 2, HSP27 Heat-Shock Proteins
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