Cobalt in the hard metal production industry: exposure via inhalation and skin and the inflammatory response in human keratinocytes

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Klasson, Maria,1977-Örebro universitet,Institutionen för medicinska vetenskaper (författare)

Cobalt in the hard metal production industry : exposure via inhalation and skin and the inflammatory response in human keratinocytes

BokEngelska2020

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Örebro :Örebro University,2020
91 s.
electronicrdacarrier

Nummerbeteckningar

LIBRIS-ID:oai:DiVA.org:oru-81944
ISBN:9789175293523
https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-81944URI

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Språk:engelska
Sammanfattning på:engelska

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Ämneskategori:vet swepub-contenttype
Ämneskategori:dok swepub-publicationtype

Serie

Örebro Studies in Medicine,1652-4063 ;220

Anmärkningar

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.

Ämnesord och genrebeteckningar

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Andra medicinska och farmaceutiska grundvetenskaper hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Other Basic Medicine hsv//eng
Cobalt
cobalt chloride
skin
HaCaT
in vitro
cell viability
pro-inflammatory cytokines
NLRP3 inflammasome

Biuppslag (personer, institutioner, konferenser, titlar ...)

Särndahl, Eva,professor,1963-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)easl (preses)
Westberg, Håkan,adjungerad professor,1949-Örebro universitet,Institutionen för naturvetenskap och teknik(Swepub:oru)hwg (preses)
Lindberg, Magnus,seniorprofessor,1952-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)mslg (preses)
Persson, Alexander,filosofie doktor,1978-Örebro universitet,Institutionen för medicinska vetenskaper(Swepub:oru)axpn (preses)
Jakobsson, Kristina,professorArbets- och miljömedicin, Institutionen för medicin, Sahlgrenska akademin, Göteborgs universitet (opponent)
Örebro universitetInstitutionen för medicinska vetenskaper (creator_code:org_t)

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