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Downregulation of lipopolysaccharide response in drosophila by negative crosstalk between the AP1 and NF-κB signaling modules

Nature Immunology volume 6, pages 211–218 (2005)Cite this article

Abstract

IκB kinase (IKK) and Jun N-terminal kinase (Jnk) signaling modules are important in the synthesis of immune effector molecules during innate immune responses against lipopolysaccharide and peptidoglycan. However, the regulatory mechanisms required for specificity and termination of these immune responses are unclear. We show here that crosstalk occurred between the drosophila Jnk and IKK pathways, which led to downregulation of each other's activity. The inhibitory action of Jnk was mediated by binding of drosophila activator protein 1 (AP1) to promoters activated by the transcription factor NF-κB. This binding led to recruitment of the histone deacetylase dHDAC1 to the promoter of the gene encoding the antibacterial protein Attacin-A and to local modification of histone acetylation content. Thus, AP1 acts as a repressor by recruiting the deacetylase complex to terminate activation of a group of NF-κB target genes.

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Figure 1: Downregulation of NF-κB signaling by Jnk in response to LPS.
Figure 2: Requirement of bsk for AttA and puc transcription.
Figure 3: The AP1 complex is involved in negative regulation of NF-κB-dependent genes.
Figure 4: dAP1 binds to the proximal sequence of the AttA promoter in vitro.
Figure 5: Binding of dAP1 to the proximal region of the AttA promoter recruits dHDAC1.
Figure 6: dAP1-mediated dHDAC1 recruitment to the AttA promoter.
Figure 7: Specificity of dAP1-mediated downregulation of the NF-κB target promoter.

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Acknowledgements

We thank W.J. Lee (Ewha Womans University, Seoul, Korea) for providing immunocompetent SL2 cells; J.L. Imler (Institute de Biologie Moleculaire et Cellulaire, Strasbourg, France) for providing reporter plasmids; and J.M. Park (University of California at San Diego) for helpful advice. BRB-ArrayTools v3.X developed by R. Simon (National Cancer Institutes of Health, Bethesda, Maryland) and A. Peng Lam (EMMES, Rockville, Maryland) were used for microarray analyses. Supported by the Creative Research Initiatives Program of the Korean Ministry of Science and Technology (Y.-J.K.).

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Authors and Affiliations

  1. Department of Biochemistry, Yonsei University, Seoul, 120-749, South Korea

    Taeil Kim, Joonsun Yoon, Hwansung Cho, Wook-bin Lee, Joon Kim & Young-Joon Kim

  2. Digital Genomics, Seoul, 120-749, South Korea

    Young-Hwa Song, Se Nyun Kim & Jeong Ho Yoon

  3. Department of Molecular Biology, Sejong University, Seoul, 143-747, South Korea

    Jeongsil Kim-Ha

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Y.H. Song, S.N. Kim and J.H. Yoon are employed by Digital Genomics.

Supplementary information

Supplementary Fig. 1

Anti-MED20 specifically recognized drosophila MED20. (PDF 159 kb)

Supplementary Table 1

DNA chip analysis of LPS response if SL2 cells and the effect of cyclohexamide on LPS induction. (PDF 97 kb)

Supplementary Table 2

Expression profile defects of the LPS induced genes in the imd-, bsk- and Rel-RNAi treated cells. (PDF 119 kb)

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Kim, T., Yoon, J., Cho, H. et al. Downregulation of lipopolysaccharide response in drosophila by negative crosstalk between the AP1 and NF-κB signaling modules. Nat Immunol 6, 211–218 (2005). https://doi.org/10.1038/ni1159

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