Effects of anthrax lethal toxin on human primary keratinocytes

S S Koçer1, M Matic, M Ingrassia

  • 1Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, New York, NY 11794-8691, USA.

Abstract

Insights

Human skin cells (keratinocytes) resist anthrax lethal toxin (LeTx) cell death. While LeTx cleaves key signaling proteins (MEKs), this doesn't cause toxicity, but paradoxically increases RANTES, potentially attracting immune cells.

Area of Science:

  • Dermatology
  • Immunology
  • Toxicology

Background:

  • Anthrax lethal toxin (LeTx) is known to affect cellular processes.
  • The impact of LeTx on human primary keratinocytes, the main cells in the epidermis, is not fully understood.
  • Previous studies suggest LeTx may have anti-inflammatory effects.

Purpose of the Study:

  • To investigate the effects of anthrax lethal toxin (LeTx) on human primary keratinocytes.
  • To determine if LeTx induces cytotoxicity in keratinocytes.
  • To examine the impact of LeTx on mitogen-activated protein kinase kinases (MEKs) and cytokine expression in keratinocytes.

Main Methods:

  • Exposure of human primary keratinocytes to anthrax lethal toxin (LeTx).
  • Analysis of MEK cleavage and subsequent proteasomal degradation.
  • Measurement of cytokine concentrations in cell culture supernatant.

Main Results:

  • Human primary keratinocytes demonstrated resistance to LeTx-induced cytotoxicity.
  • Mitogen-activated protein kinase kinases (MEKs) were cleaved and degraded, but this did not correlate with cell death.
  • LeTx reduced concentrations of several cytokines, but significantly upregulated RANTES.

Conclusions:

  • Primary keratinocytes are resistant to LeTx cytotoxicity.
  • MEK cleavage by LeTx does not predict LeTx-induced cell death in keratinocytes.
  • LeTx upregulates RANTES, a chemoattractant for immune cells, potentially explaining neutrophil recruitment to infection sites despite a general downregulation of other inflammatory markers.

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