Human Keratinocyte Responses to Woodsmoke Chemicals

TL;DR

This study explores how chemicals in woodsmoke affect human skin cells, revealing harmful responses like protein cross-linking and cell damage.

Contribution

The study identifies specific woodsmoke chemicals that trigger protein cross-linking and cellular changes in keratinocytes.

Findings

Furfural induces cross-linked envelope formation without cell permeabilization.

Syringol causes cell permeabilization and increases envelope protein content.

Chemicals like furfural and syringol alter envelope protein profiles and increase keratin content.

Abstract

Air pollution consists
of complex mixtures of chemicals with serious
deleterious health effects from acute and chronic exposure. To help
understand the mechanisms by which adverse effects occur, the present
work examines the responses of cultured human epidermal keratinocytes
to specific chemicals commonly found in woodsmoke. Our earlier findings
with liquid smoke flavoring (aqueous extract of charred wood) revealed
that such extracts stimulated the expression of genes associated with
oxidative stress and proinflammatory response, activated the aryl
hydrocarbon receptor, thereby inducing cytochrome P4501A1 activity,
and induced cross-linked envelope formation, a lethal event ordinarily
occurring during terminal differentiation. The present results showed
that furfural produced transcriptional responses resembling those
of liquid smoke, cyclohexanedione activated the aryl hydrocarbon receptor,
and several chemicals induced envelope formation. Of these, syringol
permeabilized the cells to the egress of lactate dehydrogenase at
a concentration close to that yielding envelope formation, while furfural
induced envelope formation without permeabilization detectable in
this way. Furfural (but not syringol) stimulated the incorporation
of amines into cell proteins in extracts in the absence of transglutaminase
activity. Nevertheless, both chemicals substantially increased the
amount of cellular protein incorporated into envelopes and greatly
altered the envelope protein profile. Moreover, the proportion of
keratin in the envelopes was dramatically increased. These findings
are consistent with the chemically induced protein cross-linking in
the cells. Elucidating mechanisms
by which this phenomenon occurs may help understand how smoke chemicals
interact with proteins to elicit cellular responses, interpret bioassays
of complex pollutant mixtures, and suggest additional sensitive ways
to monitor exposures.

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