Format

Send to

Choose Destination
J Cell Commun Signal. 2018 Sep;12(3):615-624. doi: 10.1007/s12079-018-0464-4. Epub 2018 Apr 28.

A network map of IL-33 signaling pathway.

Author information

1
Institute of Bioinformatics, International Technology Park, Bangalore, India. sneha@yenepoya.edu.in.
2
Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India. sneha@yenepoya.edu.in.
3
Center for Systems Biology and Molecular Medicine, Yenepoya (Deemed to be University), Mangalore, India.
4
Computational Biology Group, Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India.
5
Institute of Bioinformatics, International Technology Park, Bangalore, India.
6
Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India.
7
National Centre for Cell Science, S.P. Pune University Campus, Pune, India.
8
Institute of Bioinformatics, International Technology Park, Bangalore, India. pandey@jhmi.edu.
9
Manipal Academy of Higher Education (MAHE), Manipal, Karnataka, India. pandey@jhmi.edu.
10
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA. pandey@jhmi.edu.
11
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD, USA. pandey@jhmi.edu.
12
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. pandey@jhmi.edu.
13
Department of Oncology, Johns Hopkins University School of Medicine, 733, N Broadway, MRB 527, Baltimore, MD, USA. pandey@jhmi.edu.

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 .

KEYWORDS:

Immune response; Inflammation; NetSlim; Post-translational modifications; Pro-inflammatory cytokine; Protein-protein interactions

Supplemental Content

Full text links

Icon for Springer Icon for PubMed Central
Loading ...
Support Center