PMID- 24672526 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20140327 LR - 20211021 IS - 1664-3224 (Print) IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 5 DP - 2014 TI - Definition of a Family of Tissue-Protective Cytokines Using Functional Cluster Analysis: A Proof-of-Concept Study. PG - 115 LID - 10.3389/fimmu.2014.00115 [doi] LID - 115 AB - The discovery of the tissue-protective activities of erythropoietin (EPO) has underlined the importance of some cytokines in tissue-protection, repair, and remodeling. As such activities have been reported for other cytokines, we asked whether we could define a class of tissue-protective cytokines. We therefore explored a novel approach based on functional clustering. In this pilot study, we started by analyzing a small number of cytokines (30). We functionally classified the 30 cytokines according to their interactions by using the bioinformatics tool STRING (Search Tool for the Retrieval of Interacting Genes), followed by hierarchical cluster analysis. The results of this functional clustering were different from those obtained by clustering cytokines simply according to their sequence. We previously reported that the protective activity of EPO in a model of cerebral ischemia was paralleled by an upregulation of synaptic plasticity genes, particularly early growth response 2 (EGR2). To assess the predictivity of functional clustering, we tested some of the cytokines clustering close to EPO (interleukin-11, IL-11; kit ligand, KITLG; leukemia inhibitory factor, LIF; thrombopoietin, THPO) in an in vitro model of human neuronal cells for their ability to induce EGR2. Two of these, LIF and IL-11, induced EGR2 expression. Although these data would need to be extended to a larger number of cytokines and the biological validation should be done using more robust in vivo models, rather then just one cell line, this study shows the feasibility of this approach. This type of functional cluster analysis could be extended to other fields of cytokine research and help design biological experiments. FAU - Mengozzi, Manuela AU - Mengozzi M AD - Brighton and Sussex Medical School , Falmer , UK. FAU - Ermilov, Peter AU - Ermilov P AD - Brighton and Sussex Medical School , Falmer , UK. FAU - Annenkov, Alexander AU - Annenkov A AD - Bone and Joint Research Unit, Bart's and The London School of Medicine, William Harvey Research Institute, Queen Mary University of London , London , UK. FAU - Ghezzi, Pietro AU - Ghezzi P AD - Brighton and Sussex Medical School , Falmer , UK. FAU - Pearl, Frances AU - Pearl F AD - Translational Drug Discovery Group, School of Life Sciences, University of Sussex , Falmer , UK. LA - eng PT - Journal Article DEP - 20140317 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 PMC - PMC3955874 OTO - NOTNLM OT - EGR2 OT - bioinformatics OT - cluster analysis OT - cytokines OT - early genes OT - neuroprotection OT - repair OT - tissue-protection EDAT- 2014/03/29 06:00 MHDA- 2014/03/29 06:01 PMCR- 2014/01/01 CRDT- 2014/03/28 06:00 PHST- 2013/12/20 00:00 [received] PHST- 2014/03/05 00:00 [accepted] PHST- 2014/03/28 06:00 [entrez] PHST- 2014/03/29 06:00 [pubmed] PHST- 2014/03/29 06:01 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2014.00115 [doi] PST - epublish SO - Front Immunol. 2014 Mar 17;5:115. doi: 10.3389/fimmu.2014.00115. eCollection 2014.