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A network map of IL-33 signaling pathway

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Journal of Cell Communication and Signaling Aims and scope

Abstract

Interleukin-33 (IL-33) is a member of the IL-1 family of cytokines that play a central role in the regulation of immune responses. Its release from epithelial and endothelial cells is mediated by pro-inflammatory cytokines, cell damage and by recognition of pathogen-associated molecular patterns (PAMPs). The activity of IL-33 is mediated by binding to the IL-33 receptor complex (IL-33R) and activation of NF-κB signaling via the classical MyD88/IRAK/TRAF6 module. IL-33 also induces the phosphorylation and activation of ERK1/2, JNK, p38 and PI3K/AKT signaling modules resulting in the production and release of pro-inflammatory cytokines. Aberrant signaling by IL-33 has been implicated in the pathogenesis of several acute and chronic inflammatory diseases, including asthma, atopic dermatitis, rheumatoid arthritis and ulcerative colitis among others. Considering the biomedical importance of IL-33, we developed a pathway resource of signaling events mediated by IL-33/IL-33R in this study. Using data mined from the published literature, we describe an integrated pathway reaction map of IL-33/IL-33R consisting of 681 proteins and 765 reactions. These include information pertaining to 19 physical interaction events, 740 enzyme catalysis events, 6 protein translocation events, 4 activation/inhibition events, 9 transcriptional regulators and 2492 gene regulation events. The pathway map is publicly available through NetPath (http://www.netpath.org/), a resource of human signaling pathways developed previously by our group. This resource will provide a platform to the scientific community in facilitating identification of novel therapeutic targets for diseases associated with dysregulated IL-33 signaling. Database URL: http://www.netpath.org/pathways?path_id=NetPath_120.

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Fig. 1

Abbreviations

IL-1:

Interleukin-1

IL-33:

Interleukin-33

PAMPs:

Pathogen-associated molecular patterns

DAMP:

Danger-associated molecular patterns

IL-33R:

IL-33 receptor complex

NF-κB:

Nuclear factor-κB

TRAF6:

TNF receptor associated factor 6

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Acknowledgements

We thank the Department of Biotechnology (DBT), Government of India for research support to the Institute of Bioinformatics.SMP is a recipient of INSPIRE Faculty Award from Department of Science and Technology (DST), Government of India. RR is a recipient of SERB Young Scientist award from Department of Science and Technology (DST), Government of India. JA is a recipient of Senior Research Fellowship from Council of Scientific and Industrial Research (CSIR), Government of India. OC is a recipient of INSPIRE Fellowship from the Department of Science and Technology, Government of India.

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  1. Sneha M. Pinto

    Present address: Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India

Authors and Affiliations

  1. Institute of Bioinformatics, International Technology Park, Bangalore, India

    Sneha M. Pinto, Oishi Chatterjee, Jayshree Advani, Aneesha Radhakrishnan, T. S. Keshava Prasad & Akhilesh Pandey

  2. Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India

    Yashwanth Subbannayya, D. A. B. Rex & T. S. Keshava Prasad

  3. Computational Biology Group, Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India

    Rajesh Raju

  4. Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India

    Jayshree Advani & Akhilesh Pandey

  5. National Centre for Cell Science, S.P. Pune University Campus, Pune, India

    Mohan R. Wani

  6. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Akhilesh Pandey

  7. Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Akhilesh Pandey

  8. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Akhilesh Pandey

  9. Department of Oncology, Johns Hopkins University School of Medicine, 733, N Broadway, MRB 527, Baltimore, MD, USA

    Akhilesh Pandey

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  1. Sneha M. Pinto
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Electronic supplementary material

Supplementary Table 1

A list of protein-protein interactions identified to be involved in IL-33 signaling based on the STRING analysis tool version 10.5. Only those protein-protein interactions that are experimentally determined with a medium confidence score threshold of 0.4 and above have been considered. (XLSX 88 kb)

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Pinto, S.M., Subbannayya, Y., Rex, D.A.B. et al. A network map of IL-33 signaling pathway. J. Cell Commun. Signal. 12, 615–624 (2018). https://doi.org/10.1007/s12079-018-0464-4

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