Effects of anthrax lethal toxin on human primary keratinocytes.
OBJECTIVE
To investigate the effects of anthrax lethal toxin (LeTx) on human primary keratinocytes.


RESULTS
We show here that human primary keratinocytes are resistant to LeTx-triggered cytotoxicity. All but one of the MEKs (mitogen-activated protein kinase kinases) are cleaved within 3 h, and the cleavage of MEKs in keratinocytes leads to their subsequent proteasome-mediated degradation at different rates. Moreover, LeTx reduced the concentration of several cytokines except RANTES in culture.


CONCLUSIONS
Our results indicate that primary keratinocytes are resistant to LeTx cytotoxicity, and MEK cleavage does not correlate with LeTx cytotoxicity. Although LeTx is considered as an anti-inflammatory agent, it upregulates RANTES.


CONCLUSIONS
According to a current view, the action of LeTx results in downregulation of the inflammatory response, as evidenced by diminished expression of several inflammatory biomarkers. Paradoxically, LeTx has been reported to attract neutrophils to cutaneous infection sites. This paper, which shows that RANTES, a chemoattractant for immune cells, is upregulated after exposure of keratinocytes to LeTx, although a number of other markers of the inflammatory response are downregulated. Our results might explain why the exposure of keratinocytes to LeTx results in the recruitment of neutrophils to cutaneous infection sites, while the expression of several inflammatory biomarkers is diminished.
Koçer
S S
SS
Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, New York, NY 11794-8691, USA.
Matic
M
M
Ingrassia
M
M
Walker
S G
SG
Roemer
E
E
Licul
G
G
Simon
S R
SR
D000818:Animals; D000942:Antigens, Bacterial / Q000494:pharmacology* / Q000633:toxicity*; D001408:Bacillus anthracis; D001427:Bacterial Toxins / Q000494:pharmacology* / Q000633:toxicity*; D015415:Biomarkers / Q000378:metabolism; D018946:Chemokine CCL5 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D052816:Foreskin; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D015415:Biomarkers; D018946:Chemokine CCL5; D016207:Cytokines; D006023:Glycoproteins; C030325:anthrax toxin; C039304:calpain inhibitors; D020929:Mitogen-Activated Protein Kinase Kinases