Micrococci and peptidoglycan activate TLR2 →Myd88 →IRAK→TRAF→NIK→IKK→NF-κB signal transduction pathway that induces transcription of interleukin-8

Q. Wang, Roman Dziarski, C. J. Kirschning, M. Muzio, Dipika Gupta

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152 Citations (Scopus)

Abstract

This study was done to elucidate the signal transduction pathway of interleukin-8 (IL-8) induction by gram-positive bacteria. Bacteria (micrococci) and peptidoglycan (PGN) induced transcription of IL-8 in HEK293 cells expressing Toll-like receptor 2 (TLR2) and CD14 but not in those expressing TLR1 or TLR4. A mutation within the NF-κB site in the IL-8 promoter abrogated transcriptional induction of IL-8 by the two stimulants. Dominant negative myeloid differentiation protein (MyD88), IL-1 receptor-associated kinase (IRAK), NFκB-inducing kinase (NIK), and IκB kinase (IKK) mutant forms completely inhibited micrococcus- and PGN-induced activation of NF-κB and expression of the gene for IL-8. Induction of NF-κB was partially inhibited by dominant negative tumor necrosis factor receptor-associated kinase 6 (TRAF6) but not TRAF2, whereas induction of IL-8 gene was partially inhibited by both TRAF6 and TRAF2. These data indicate that micrococci and PGN induce TLR2-dependent activation of the gene for IL-8 and that this activation requires MyD88, IRAK, NIK, IKK, and NF-κB and may also utilize TRAF6 and, to a lesser extent, TRAF2.

Original languageEnglish
Pages (from-to)2270-2276
Number of pages7
JournalInfection and Immunity
Volume69
Issue number4
DOIs
StatePublished - 2001

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Toll-Like Receptor 2
Micrococcus
Peptidoglycan
Interleukin-8
Signal Transduction
TNF Receptor-Associated Factor 2
TNF Receptor-Associated Factor 6
Phosphotransferases
Interleukin-1 Receptor-Associated Kinases
Myeloid Differentiation Factor 88
Tumor Necrosis Factor Receptors
HEK293 Cells
Gram-Positive Bacteria
Transcriptional Activation
Bacteria
Gene Expression
Mutation
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Micrococci and peptidoglycan activate TLR2 →Myd88 →IRAK→TRAF→NIK→IKK→NF-κB signal transduction pathway that induces transcription of interleukin-8",
abstract = "This study was done to elucidate the signal transduction pathway of interleukin-8 (IL-8) induction by gram-positive bacteria. Bacteria (micrococci) and peptidoglycan (PGN) induced transcription of IL-8 in HEK293 cells expressing Toll-like receptor 2 (TLR2) and CD14 but not in those expressing TLR1 or TLR4. A mutation within the NF-κB site in the IL-8 promoter abrogated transcriptional induction of IL-8 by the two stimulants. Dominant negative myeloid differentiation protein (MyD88), IL-1 receptor-associated kinase (IRAK), NFκB-inducing kinase (NIK), and IκB kinase (IKK) mutant forms completely inhibited micrococcus- and PGN-induced activation of NF-κB and expression of the gene for IL-8. Induction of NF-κB was partially inhibited by dominant negative tumor necrosis factor receptor-associated kinase 6 (TRAF6) but not TRAF2, whereas induction of IL-8 gene was partially inhibited by both TRAF6 and TRAF2. These data indicate that micrococci and PGN induce TLR2-dependent activation of the gene for IL-8 and that this activation requires MyD88, IRAK, NIK, IKK, and NF-κB and may also utilize TRAF6 and, to a lesser extent, TRAF2.",
author = "Q. Wang and Roman Dziarski and Kirschning, {C. J.} and M. Muzio and Dipika Gupta",
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T1 - Micrococci and peptidoglycan activate TLR2 →Myd88 →IRAK→TRAF→NIK→IKK→NF-κB signal transduction pathway that induces transcription of interleukin-8

AU - Wang, Q.

AU - Dziarski, Roman

AU - Kirschning, C. J.

AU - Muzio, M.

AU - Gupta, Dipika

PY - 2001

Y1 - 2001

N2 - This study was done to elucidate the signal transduction pathway of interleukin-8 (IL-8) induction by gram-positive bacteria. Bacteria (micrococci) and peptidoglycan (PGN) induced transcription of IL-8 in HEK293 cells expressing Toll-like receptor 2 (TLR2) and CD14 but not in those expressing TLR1 or TLR4. A mutation within the NF-κB site in the IL-8 promoter abrogated transcriptional induction of IL-8 by the two stimulants. Dominant negative myeloid differentiation protein (MyD88), IL-1 receptor-associated kinase (IRAK), NFκB-inducing kinase (NIK), and IκB kinase (IKK) mutant forms completely inhibited micrococcus- and PGN-induced activation of NF-κB and expression of the gene for IL-8. Induction of NF-κB was partially inhibited by dominant negative tumor necrosis factor receptor-associated kinase 6 (TRAF6) but not TRAF2, whereas induction of IL-8 gene was partially inhibited by both TRAF6 and TRAF2. These data indicate that micrococci and PGN induce TLR2-dependent activation of the gene for IL-8 and that this activation requires MyD88, IRAK, NIK, IKK, and NF-κB and may also utilize TRAF6 and, to a lesser extent, TRAF2.

AB - This study was done to elucidate the signal transduction pathway of interleukin-8 (IL-8) induction by gram-positive bacteria. Bacteria (micrococci) and peptidoglycan (PGN) induced transcription of IL-8 in HEK293 cells expressing Toll-like receptor 2 (TLR2) and CD14 but not in those expressing TLR1 or TLR4. A mutation within the NF-κB site in the IL-8 promoter abrogated transcriptional induction of IL-8 by the two stimulants. Dominant negative myeloid differentiation protein (MyD88), IL-1 receptor-associated kinase (IRAK), NFκB-inducing kinase (NIK), and IκB kinase (IKK) mutant forms completely inhibited micrococcus- and PGN-induced activation of NF-κB and expression of the gene for IL-8. Induction of NF-κB was partially inhibited by dominant negative tumor necrosis factor receptor-associated kinase 6 (TRAF6) but not TRAF2, whereas induction of IL-8 gene was partially inhibited by both TRAF6 and TRAF2. These data indicate that micrococci and PGN induce TLR2-dependent activation of the gene for IL-8 and that this activation requires MyD88, IRAK, NIK, IKK, and NF-κB and may also utilize TRAF6 and, to a lesser extent, TRAF2.

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