PMID- 33163760 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20201112 IS - 2470-1343 (Electronic) IS - 2470-1343 (Linking) VI - 5 IP - 43 DP - 2020 Nov 3 TI - Epigenetic Studies Revealed a Ghost Proteome in PC1/3 KD Macrophages under Antitumoral Resistance Induced by IL-10. PG - 27774-27782 LID - 10.1021/acsomega.0c02530 [doi] AB - Our previous investigation on macrophages has allowed us to show that the inhibition of the enzyme proprotein convertase (PC1/3) controls the activation of macrophages. We demonstrated that PC1/3 knockdown (KD) in macrophages exhibits an increased secretion of proinflammatory and antitumoral factors. In this biological context, we assessed the presence of histone modifications and the presence and contribution of a "ghost proteome" in these macrophages. We identified a set of alternative proteins (AltProts) that have a key role in the regulation of various signaling pathways. In this study, to further investigate the underlying mechanisms involved in the resistance of PC1/3-KD macrophages to anti-inflammatory stimuli, we have conducted a proteomic system biology study to assess the epigenome variation, focusing on histone modifications. Results from our study have indicated the presence of significant variations in histone modifications along with the identification of 28 AltProts, which can be correlated with antitumoral resistance under IL-10 stimulation. These findings highlight a key role of altered epigenome histone modifications in driving resistance and indicate that like the reference proteins, AltProts can have a major impact in the field of epigenetics and regulation of gene expression, as shown in our results. FAU - Cardon, Tristan AU - Cardon T AD - Inserm, CHRU Lille, University Lille, U-1192-Laboratoire Proteomique, Reponse Inflammatoire et Spectrometrie de Masse-PRISM, Lille 59000, France. FAU - Ozcan, Bilgehan AU - Ozcan B AD - Inserm, CHRU Lille, University Lille, U-1192-Laboratoire Proteomique, Reponse Inflammatoire et Spectrometrie de Masse-PRISM, Lille 59000, France. FAU - Aboulouard, Soulaimane AU - Aboulouard S AD - Inserm, CHRU Lille, University Lille, U-1192-Laboratoire Proteomique, Reponse Inflammatoire et Spectrometrie de Masse-PRISM, Lille 59000, France. FAU - Kobeissy, Firas AU - Kobeissy F AD - Department of Psychiatry, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, United States. FAU - Duhamel, Marie AU - Duhamel M AD - Inserm, CHRU Lille, University Lille, U-1192-Laboratoire Proteomique, Reponse Inflammatoire et Spectrometrie de Masse-PRISM, Lille 59000, France. FAU - Rodet, Franck AU - Rodet F AD - Inserm, CHRU Lille, University Lille, U-1192-Laboratoire Proteomique, Reponse Inflammatoire et Spectrometrie de Masse-PRISM, Lille 59000, France. FAU - Fournier, Isabelle AU - Fournier I AD - Inserm, CHRU Lille, University Lille, U-1192-Laboratoire Proteomique, Reponse Inflammatoire et Spectrometrie de Masse-PRISM, Lille 59000, France. AD - Institut Universitaire de France, Paris 75000, France. FAU - Salzet, Michel AU - Salzet M AD - Inserm, CHRU Lille, University Lille, U-1192-Laboratoire Proteomique, Reponse Inflammatoire et Spectrometrie de Masse-PRISM, Lille 59000, France. AD - Institut Universitaire de France, Paris 75000, France. LA - eng PT - Journal Article DEP - 20201001 PL - United States TA - ACS Omega JT - ACS omega JID - 101691658 PMC - PMC7643081 COIS- The authors declare no competing financial interest. EDAT- 2020/11/10 06:00 MHDA- 2020/11/10 06:01 PMCR- 2020/10/01 CRDT- 2020/11/09 05:34 PHST- 2020/05/29 00:00 [received] PHST- 2020/09/18 00:00 [accepted] PHST- 2020/11/09 05:34 [entrez] PHST- 2020/11/10 06:00 [pubmed] PHST- 2020/11/10 06:01 [medline] PHST- 2020/10/01 00:00 [pmc-release] AID - 10.1021/acsomega.0c02530 [doi] PST - epublish SO - ACS Omega. 2020 Oct 1;5(43):27774-27782. doi: 10.1021/acsomega.0c02530. eCollection 2020 Nov 3.