Chloromethyl ketones inhibit interleukin-12 production in mouse macrophages stimulated with lipopolysaccharide

B. Y. Kang, S. W. Chung, S. Y. Im, S. Y. Hwang, Tae Sung Kim

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Interleukin-12 (IL-12) plays a pivotal role in the development of T-helper type 1 (Th1) immune response, which may be involved in the pathogenesis of chronic inflammatory autoimmune disorders. In this study, we investigated the effects of N-α-tosyl-L-phenylalanine chloromethyl ketone (TPCK) and N-α-tosyl-L-lysine chloromethyl ketone (TLCK), serine protease inhibitors, on the production of IL-12 from macrophages stimulated with lipopolysaccharide (LPS). TPCK and TLCK potently inhibited this LPS-induced IL-12 production in a dose-dependent manner. The effect of TPCK and TLCK on the IL-12 p40 promoter activation was analyzed by transfecting monocytic RAW264.7 cells with p40 promoter-reporter constructs. The repressive effect maps to a region in the p40 promoter containing a binding site for NFκB (p40-κB). A linker scan mutant of the p40-κB site abrogates the inhibitory effect on the p40 promoter, confirming the functional relevance of the NFκB site. Our results show that TPCK and TLCK inhibit NFκB-mediated IL-12 production in macrophages. Copyright (C) 1999 Elsevier Science B.V.

Original languageEnglish
Pages (from-to)135-138
Number of pages4
JournalImmunology Letters
Volume70
Issue number2
DOIs
Publication statusPublished - 1999 Nov 1
Externally publishedYes

Fingerprint

Interleukin-12
Ketones
Lipopolysaccharides
Macrophages
Phenylalanine
Lysine
Serine Proteinase Inhibitors
adjuvant P40
Binding Sites
lysine chloromethyl ketone

Keywords

  • Interleukin-12
  • NFκB
  • Serine protease inhibitor

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

Cite this

Chloromethyl ketones inhibit interleukin-12 production in mouse macrophages stimulated with lipopolysaccharide. / Kang, B. Y.; Chung, S. W.; Im, S. Y.; Hwang, S. Y.; Kim, Tae Sung.

In: Immunology Letters, Vol. 70, No. 2, 01.11.1999, p. 135-138.

Research output: Contribution to journalArticle

Kang, B. Y. ; Chung, S. W. ; Im, S. Y. ; Hwang, S. Y. ; Kim, Tae Sung. / Chloromethyl ketones inhibit interleukin-12 production in mouse macrophages stimulated with lipopolysaccharide. In: Immunology Letters. 1999 ; Vol. 70, No. 2. pp. 135-138.
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