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

B. Y. Kang; S. W. Chung; S. Y. Im; S. Y. Hwang; T. S. Kim

doi:10.1016/S0165-2478(99)00136-4

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

B. Y. Kang, S. W. Chung, S. Y. Im, S. Y. Hwang, T. S. Kim

Research output: Contribution to journal › Article › peer-review

13 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 language	English
Pages (from-to)	135-138
Number of pages	4
Journal	Immunology Letters
Volume	70
Issue number	2
DOIs	https://doi.org/10.1016/S0165-2478(99)00136-4
Publication status	Published - 1999 Nov 1
Externally published	Yes

Bibliographical note

Funding Information:
We thank Drs S. Wolf (Genetics Institute, USA), G. Trinchieri (Wistar Institute, USA), D.T. Umetsu (Stanford University, USA), Y.K. Choe (KRIBB, Korea) for providing reagents. This work was supported by Grants from the Korea Science and Engineering Foundation (HRC to T.S. Kim and S.-Y. Im).

Keywords

Interleukin-12
NFκB
Serine protease inhibitor

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1016/S0165-2478(99)00136-4

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title = "Chloromethyl ketones inhibit interleukin-12 production in mouse macrophages stimulated with lipopolysaccharide",

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.",

keywords = "Interleukin-12, NFκB, Serine protease inhibitor",

author = "Kang, {B. Y.} and Chung, {S. W.} and Im, {S. Y.} and Hwang, {S. Y.} and Kim, {T. S.}",

note = "Funding Information: We thank Drs S. Wolf (Genetics Institute, USA), G. Trinchieri (Wistar Institute, USA), D.T. Umetsu (Stanford University, USA), Y.K. Choe (KRIBB, Korea) for providing reagents. This work was supported by Grants from the Korea Science and Engineering Foundation (HRC to T.S. Kim and S.-Y. Im).",

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AU - Im, S. Y.

AU - Hwang, S. Y.

AU - Kim, T. S.

N1 - Funding Information: We thank Drs S. Wolf (Genetics Institute, USA), G. Trinchieri (Wistar Institute, USA), D.T. Umetsu (Stanford University, USA), Y.K. Choe (KRIBB, Korea) for providing reagents. This work was supported by Grants from the Korea Science and Engineering Foundation (HRC to T.S. Kim and S.-Y. Im).

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N2 - 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.

AB - 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.

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

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