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Dose- and time-dependent changes in viability and IL-6, CXCL8 and CCL2 production by HaCaT-cells exposed to cobalt: Effects of high and low calcium growth conditions
Örebro University, School of Medical Sciences. Department of Occupational and Environmental Medicine, University Hospital Örebro, Örebro, Sweden.
Örebro University, School of Medical Sciences. Department of Dermatology, University Hospital Örebro, Örebro, Sweden.
Örebro University, School of Medical Sciences.ORCID iD: 0000-0002-4319-7208
Department of Occupational and Environmental Medicine, University Hospital Örebro, Örebro, Sweden.
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(English)Manuscript (preprint) (Other academic)
National Category
Other Basic Medicine
Identifiers
URN: urn:nbn:se:oru:diva-85681OAI: oai:DiVA.org:oru-85681DiVA, id: diva2:1466424
Available from: 2020-09-11 Created: 2020-09-11 Last updated: 2020-09-11Bibliographically approved
In thesis
1. Cobalt in the hard metal production industry: exposure via inhalation and skin and the inflammatory response in human keratinocytes
Open this publication in new window or tab >>Cobalt in the hard metal production industry: exposure via inhalation and skin and the inflammatory response in human keratinocytes
2020 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cobalt is a strong sensitizer and can cause contact allergy upon both direct contact or from airborne exposure on the skin. In the skin, keratinocytes are the first cells to come in contact with the metal and will react and respond to the danger by triggering an alarm system resulting in an inflammatory response in the skin. Keratinocytes have been shown to produce IL-1β, which is one of the most potent  inflammatory agents in our body and is associated with a variety of diseases.

The aims of this thesis was to investigate cobalt air concentrations for different particle fractions for possible use as proxies for other article measures and to examine if cobalt skin and inhalable air exposure contributes to uptake. Also, to investigate the effect of cobalt on cultured human keratinocyte cell viability, pro-inflammatory cytokine/chemokine release and NLRP3 inflammasome activation using cells cultured at low or high calcium (the latter yielding a more differentiated cell type).

Air exposure to cobalt was found in all departments and for all work tasks in the hard metal production facility and exposures were in general below the Swedish OEL for inhalable cobalt. The highest exposure levels were found in the powder production department and for laboratory and furnace work. Good correlations for the mass based measures enable us to use the findings for future references. When personal inhalable air levels of cobalt, cobalt skin levels skin and biological monitoring of cobalt in blood were analysed, the skin exposure was determined to be import as a route of uptake. Skin exposure to cobalt in the hard metal industry, could further affect the total uptake in the same order of magnitude as air exposure. In vitro investigations of cobalt using the human keratinocyte cell line HaCaT, showed that CoCl2 triggered an alarm system in cells where the proinflammatory cytokines/chemokines IL-6, CXCL8 and CCL2, known to be involved in skin inflammation, were secreted in a time- and dosedependent manner. Comparing HaCaT cells of high- and low differentiation stages indicated that the effect of cobalt chloride on cell toxicity occurs throughout the living epidermis. CoCl2 exposure also resulted in secretion of the proinflammatory cytokines IL-1β and IL-18, and caspase-1, which indicates activation of the NLRP3 inflammasome in the cells. CoCl2 regulates the inflammasome both as primer and as an activator. Our mRNA results indicates a negative feedback mechanism in the inflamamsome due to the exposure. The inflammatory response in general is more dose than time dependent, which be important for understanding the mechanisms of allergic sensitization.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2020. p. 91
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 220
Keywords
Cobalt, cobalt chloride, skin, HaCaT, in vitro, cell viability, pro-inflammatory cytokines, NLRP3 inflammasome
National Category
Other Basic Medicine
Identifiers
urn:nbn:se:oru:diva-81944 (URN)978-91-7529-352-3 (ISBN)
Public defence
2020-10-09, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 13:00 (Swedish)
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Available from: 2020-05-19 Created: 2020-05-19 Last updated: 2020-09-28Bibliographically approved

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Klasson, MariaLindberg, MagnusSärndahl, EvaPersson, Alexander

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