A network map of IL-33 signaling pathway

Sneha M. Pinto, Yashwanth Subbannayya, D. A.B. Rex, Rajesh Raju, Oishi Chatterjee, Jayshree Advani, Aneesha Radhakrishnan, T. S. Keshava Prasad, Mohan R. Wani, Akhilesh Pandey

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)615-624
Number of pages10
JournalJournal of Cell Communication and Signaling
Volume12
Issue number3
DOIs
StatePublished - Sep 1 2018

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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