Protease inhibitors protect macrophages from lipopolysaccharide-induced cytotoxicity: Possible role for NF-κB

Aida Abate, Henning Schroeder

Research output: Contribution to journalArticlepeer-review

28 Scopus citations


Recent studies suggest lipopolysaccharide (LPS) mediated cell death as underlying mechanism of hyporesponsiveness and dysfunction of macrophages in the late phase of septic shock. In the present study LPS (0.001-30 μg/ml) caused a concentration-dependent toxicity in the macrophage cell line (J774.1A) within 24 h. The toxicity induced by LPS (1 μg/ml) was completely inhibited by the serine protease inhibitors, N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-α-tosyl-L-lysine chloromethyl ketone (TLCK) as measured by the mitochondrial-dependent oxidation of 3-(4,5-dimethyl-thiazol-2-yl)-2,5 -diphenyltetrazolium bromid (MTT) to formazan. These inhibitors antagonize the activation of nuclear transcription factor-κB (NF-κB) indirectly by inhibiting IκBα-protease. SN50, a direct inhibitor of NF-κB translocation into the nucleus also protected macrophages from LPS-mediated toxicity. We conclude from these data that the early phase signal transduction pathway leading to LPS-mediated cytotoxicity in macrophages involves the activation of NF-κB. Thus, IκBα-protease inhibitors might serve as therapeutical agents to maintain macrophage viability during sepsis and to prevent sepsis-induced immune dysfunction.

Original languageEnglish (US)
Pages (from-to)1081-1088
Number of pages8
JournalLife Sciences
Issue number12
StatePublished - Feb 13 1998
Externally publishedYes


  • Cytotoxicity
  • Lipopolysaccharide
  • Macrophages
  • NF-κB
  • Serine protease inhibitors

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