UVB and Proinflammatory Cytokines Synergistically Activate TNF-α Production in Keratinocytes Through Enhanced Gene Transcription
Open accessAbstract
UVB irradiation potently induces cytokines in the skin, including IL-1alpha and tumor necrosis factor-alpha (TNF-alpha). The mechanism for TNF-alpha induction in UVB-irradiated keratinocytes is not clear. In this study, we explored the effects of UVB and cytokines, alone or in combination in human keratinocytes. Keratinocytes were sham- or UVB-irradiated with 30 mJ cm(-2), and then incubated in the absence or presence of IFN-alpha2b, TNF-alpha, or IL-1alpha. UVB and IL-1alpha treatment synergistically enhanced TNF-alpha secretion and mRNA levels in human keratinocytes, similar to the findings reported previously in human fibroblasts. Exogenous recombinant TNF-alpha up-regulates its own mRNA level. However, addition of IFN-alpha2b did not show any additive effect on TNF-alpha mRNA induction. To understand the regulation of TNF-alpha mRNA by UVB, with or without IL-1alpha, we examined the transcription rate and half-life of TNF-alpha mRNA. Treatment of keratinocytes with IL-1alpha or UVB alone increased TNF-alpha gene transcription 4- to 5-fold over sham treatment, and TNF-alpha gene transcription increased 11-fold in cells treated with UVB plus IL-1alpha over sham. UVB with IL-1alpha did not enhance the half-life of TNF-alpha mRNA over that seen with UVB alone. In conclusion, TNF-alpha expression in primary keratinocytes is upregulated transcriptionally by UVB and IL-1alpha.
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DNA damage-induced replication and transcriptional stress induces pro-inflammatory cytokines.
“DNA damage-induced replication and transcriptional stress induces pro-inflammatory cytokines ( 21 , 31 – 33 )”
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 [32]
The Discussion reports that UVB induces pro-inflammatory cytokines, including TNF-α, IL-1 and IL-6, in keratinocytes. It does not establish that DNA damage-induced replication or transcriptional stress causes that induction; the Discussion says the mechanism of UVB-induced TNF-α transcription has not yet been defined. Page numbers were not available in our copy. (LLM, conf=0.84)
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- Authors
- Bashir, M. M., Sharma, M. R., & Werth, V. P.
- Affiliations
- Philadelphia VA Medical Center (US)
- Corresponding author
- Werth, Victoria P.
- Venue
- Journal of Investigative Dermatology
- Publisher
- Elsevier BV
- Published
- 2009-04
- Volume
- 129
- Issue
- 4
- Pages
- 994-1001
- ISSN
- 0022-202X (ISSN-L)
- PMC
- PMC3345265
- OpenAlex
- W2023953437
- Cited by
- 153
- References
- 53
- Citations by year
- 2026: 12 · 2025: 14 · 2024: 10 · 2023: 14 · 2022: 8 · 2021: 12 · 2020: 17 · 2019: 13 · 2018: 7 · 2017: 6 · 2016: 5 · 2015: 9 · 2014: 8 · 2013: 7
- FWCI
- 3.57
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Journal of Investigative Dermatology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (P30AR057217)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Dermatology › Dermatology and Skin Diseases
- Life Sciences › Immunology and Microbiology › Immunology › Psoriasis: Treatment and Pathogenesis
- Keywords
- UVB irradiation, TNF-α, keratinocytes, interleukin-1 alpha, interferon alfa-2b, inflammatory cytokines, gene transcription, mRNA half-life, cytokine synergy, skin inflammation
- MeSH terms
- Cells, Cultured, Gene Expression Regulation, Humans, RNA, Messenger, Transcription, Genetic, Tumor Necrosis Factor-alpha, Ultraviolet Rays, Keratinocytes, Interferon-alpha, Interleukin-1alpha
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