Journal article
HaCaT Keratinocytes Overexpressing the S100 Proteins S100A8 and S100A9 Show Increased NADPH Oxidase and NF-κB Activities
Journal of investigative dermatology, Vol.127(8), pp.2001-2011
08/2007
DOI: 10.1038/sj.jid.5700820
PMID: 17429438
Abstract
The calcium- and arachidonic acid (AA)-binding proteins S100A8 and S100A9 are involved in nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation in phagocytes. They are specifically expressed in myeloid cells, and are also found in epithelial cells in various (patho)physiological conditions. We have investigated the consequences of S100A8/A9 overexpression in epithelial cell lines on reactive oxygen species (ROS) generation and downstream signaling. Epithelial carcinoma HeLa cells, which exclusively express Nox2, showed dramatically increased activation of NADPH oxidase by phorbol 12-myristate 13-acetate after S100A8/A9 gene transfection. HaCaT keratinocytes overexpressing S100A8/A9 showed enhanced, transient ROS generation in response to the calcium ionophore A23187 compared to mock-transfected cells. Polymerase chain reaction analysis revealed mRNA transcripts for Nox1, Nox2, and Nox5 in HaCaT keratinocytes. Detailed transfection studies confirmed that NADPH oxidase activities in Nox1- and Nox5-transfected HeLa cells were enhanced after S100A8/A9 gene complementation. Furthermore, mutational analysis revealed that AA binding and Thr113 phosphorylation are important for S100A8/A9-enhanced activation of NADPH oxidase. Nuclear factor-κB (NF-κB) activation and interleukin-8 mRNA levels were increased in S100A8/A9-HaCaT keratinocytes, consistent with the view that NF-κB is a redox-sensitive transcription factor. Because they are expressed in epithelia under specific conditions, S100A8 and S100A9 might be involved in skin pathogenesis by modulating aspects of downstream signaling.
Details
- Title: Subtitle
- HaCaT Keratinocytes Overexpressing the S100 Proteins S100A8 and S100A9 Show Increased NADPH Oxidase and NF-κB Activities
- Creators
- Malgorzata Benedyk - University of MünsterClaudia Sopalla - University of MünsterWolfgang Nacken - University of MünsterGünther Bode - University of MünsterHarut Melkonyan - University of MünsterBotond Banfi - University of IowaClaus Kerkhoff - University of Münster
- Resource Type
- Journal article
- Publication Details
- Journal of investigative dermatology, Vol.127(8), pp.2001-2011
- Publisher
- Elsevier Inc
- DOI
- 10.1038/sj.jid.5700820
- PMID
- 17429438
- ISSN
- 0022-202X
- eISSN
- 1523-1747
- Language
- English
- Date published
- 08/2007
- Academic Unit
- Anatomy and Cell Biology; Otolaryngology; Internal Medicine
- Record Identifier
- 9984284326602771
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