Caspase 3 blocking avoids the expression of autoantigens triggered by apoptosis in neonatal Balb/c mice skin

Reumatismo. 2011 Mar;63(1):29-37. doi: 10.4081/reumatismo.2011.29.

Abstract

Objective: To assess the effect of caspase 3 inhibition, in the expression of intracellular antigens induced by apoptosis.

Material and methods: Skin explants of neonatal Balb/c mice were used to assess the autoantigen expression. Skin was obtained by punch biopsies, tissues were cultured in DMEM; cell death was induced by chemicals and assessed by TUNEL. The expression of La, Ro, Sm, RNP, Cajal Bodies and NuMa antigens were monitored by immunohistochemistry using autoantibodies or monoclonal antibodies against these antigens.

Results: Chemicals used to induce cell death, successfully produced apoptosis or necrosis in more than 60% of keratinocytes, and viability was significantly decreased when it was compared with those in controls. An increased expression of all skin intracellular antigens in skin biopsies treated with chemicals, major antigenic expression was detected with anti-La and anti-Ro antibodies. The caspase 3 inhibitor DEVD-CMK significantly decreased the expression of antigens induced by chemicals.

Conclusion: By this result we can infer that caspase inhibitors modify apoptosis and decrease the autoantigens associated to cell death.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Chloromethyl Ketones / pharmacology*
  • Animals
  • Animals, Newborn
  • Apoptosis / immunology*
  • Autoantigens / biosynthesis*
  • Autoimmune Diseases / etiology
  • Autoimmune Diseases / prevention & control*
  • Biopsy
  • Camptothecin / pharmacology
  • Caspase Inhibitors*
  • Cells, Cultured / drug effects
  • Cells, Cultured / enzymology
  • Cells, Cultured / immunology
  • Cycloheximide / pharmacology
  • Cysteine Proteinase Inhibitors / pharmacology
  • Cysteine Proteinase Inhibitors / therapeutic use*
  • Drug Evaluation, Preclinical
  • Hydrogen Peroxide / pharmacology
  • In Situ Nick-End Labeling
  • Mercuric Chloride / pharmacology
  • Mice
  • Mice, Inbred BALB C
  • Organ Culture Techniques
  • Skin / enzymology
  • Skin / immunology*

Substances

  • Amino Acid Chloromethyl Ketones
  • Autoantigens
  • Caspase Inhibitors
  • Cysteine Proteinase Inhibitors
  • benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
  • Mercuric Chloride
  • Cycloheximide
  • Hydrogen Peroxide
  • Camptothecin