Cited by 153Skin Protection and AgingDermatology and Skin DiseasesPsoriasis: Treatment and Pathogenesis

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UVB and Proinflammatory Cytokines Synergistically Activate TNF-α Production in Keratinocytes through Enhanced Gene Transcription

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Bashir, Muhammad M., Sharma, Meena R., Werth, Victoria P.·2009·Journal of Investigative Dermatology

DOI 10.1038/jid.2008.332PMC PMC3345265

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Abstract

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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Authors: Bashir, M. M., Sharma, M. R., & Werth, V. P.
Affiliations: Philadelphia VA Medical Center (US)
Corresponding author: Werth, Victoria P.
ORCID: Bashir, Muhammad M.
Sharma, Meena R.
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)
DOI: 10.1038/jid.2008.332
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: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2436 d)
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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UVB and Proinflammatory Cytokines Synergistically Activate TNF-α Production in Keratinocytes through Enhanced Gene Transcription

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