Journal
JOURNAL OF CELL COMMUNICATION AND SIGNALING
Volume 12, Issue 3, Pages 615-624Publisher
SPRINGER
DOI: 10.1007/s12079-018-0464-4
Keywords
Immune response; Inflammation; NetSlim; Pro-inflammatory cytokine; Post-translational modifications; Protein-protein interactions
Categories
Funding
- Department of Biotechnology (DBT), Government of India
- INSPIRE Faculty Award from Department of Science and Technology (DST), Government of India
- SERB Young Scientist award from Department of Science and Technology (DST), Government of India
- Council of Scientific and Industrial Research (CSIR), Government of India
- INSPIRE Fellowship from the Department of Science and Technology, Government of India
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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-kappa B 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 proinflammatory 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/IL33R in this study. Using data mined from the published literature, we describe an integrated pathway reaction map of IL-33/IL33R 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.
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