PMID- 29084133 OWN - NLM STAT- MEDLINE DCOM- 20180608 LR - 20211204 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 18 IP - 11 DP - 2017 Oct 30 TI - Modulation of the Senescence-Associated Inflammatory Phenotype in Human Fibroblasts by Olive Phenols. LID - 10.3390/ijms18112275 [doi] LID - 2275 AB - Senescent cells display an increase in the secretion of growth factors, inflammatory cytokines and proteolytic enzymes, termed the "senescence-associated-secretory-phenotype" (SASP), playing a major role in many age-related diseases. The phenolic compounds present in extra-virgin olive oil are inhibitors of oxidative damage and have been reported to play a protective role in inflammation-related diseases. Particularly, hydroxytyrosol and oleuropein are the most abundant and more extensively studied. Pre-senescent human lung (MRC5) and neonatal human dermal (NHDF) fibroblasts were used as cellular model to evaluate the effect of chronic (4-6 weeks) treatment with 1 muM hydroxytyrosol (HT) or 10 muM oleuropein aglycone (OLE) on senescence/inflammation markers. Both phenols were effective in reducing beta-galactosidase-positive cell number and p16 protein expression. In addition, senescence/inflammation markers such as IL-6 and metalloprotease secretion, and Ciclooxigenase type 2 (COX-2) and alpha-smooth-actin levels were reduced by phenol treatments. In NHDF, COX-2 expression, Nuclear Factor kappa-light-chain-enhancer of activated B cells (NFkappaB) protein level and nuclear localization were augmented with culture senescence and decreased by OLE and HT treatment. Furthermore, the inflammatory effect of Tumor Necrosis Factor alpha (TNFalpha) exposure was almost completely abolished in OLE- and HT-pre-treated NHDF. Thus, the modulation of the senescence-associated inflammatory phenotype might be an important mechanism underlying the beneficial effects of olive oil phenols. FAU - Menicacci, Beatrice AU - Menicacci B AD - Department of Biomedical, Experimental and Clinical Science Mario Serio, Experimental Pathology and Oncology Section, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. beatrice.menicacci@stud.unifi.it. AD - Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy. beatrice.menicacci@stud.unifi.it. FAU - Cipriani, Caterina AU - Cipriani C AD - NEUROFARBA Department, Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. caterinacipriani8@gmail.com. FAU - Margheri, Francesca AU - Margheri F AD - Department of Biomedical, Experimental and Clinical Science Mario Serio, Experimental Pathology and Oncology Section, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. fmargheri@unifi.it. FAU - Mocali, Alessandra AU - Mocali A AUID- ORCID: 0000-0002-5673-1780 AD - Department of Biomedical, Experimental and Clinical Science Mario Serio, Experimental Pathology and Oncology Section, University of Florence, Viale Morgagni 50, 50134 Florence, Italy. alessandra.mocali@unifi.it. FAU - Giovannelli, Lisa AU - Giovannelli L AUID- ORCID: 0000-0002-4027-4693 AD - NEUROFARBA Department, Pharmacology and Toxicology Section, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy. lisa.giovannelli@unifi.it. LA - eng PT - Journal Article DEP - 20171030 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Biomarkers) RN - 0 (Iridoid Glucosides) RN - 0 (Iridoids) RN - 0 (Phenols) RN - 0 (Plant Extracts) RN - 2O4553545L (oleuropein) SB - IM MH - Anti-Inflammatory Agents/*pharmacology MH - Biomarkers MH - Cell Line MH - Cells, Cultured MH - Cellular Senescence/*drug effects MH - Fibroblasts/*drug effects/*metabolism MH - Humans MH - Iridoid Glucosides MH - Iridoids/metabolism MH - Olea/*chemistry MH - Phenols/*pharmacology MH - Phenotype MH - Plant Extracts/*pharmacology PMC - PMC5713245 OTO - NOTNLM OT - SASP OT - hydroxytyrosol OT - inflammatory phenotype OT - oleuropein OT - replicative senescence COIS- The authors declare no conflict of interest. EDAT- 2017/10/31 06:00 MHDA- 2018/06/09 06:00 PMCR- 2017/11/01 CRDT- 2017/10/31 06:00 PHST- 2017/09/27 00:00 [received] PHST- 2017/10/19 00:00 [revised] PHST- 2017/10/25 00:00 [accepted] PHST- 2017/10/31 06:00 [entrez] PHST- 2017/10/31 06:00 [pubmed] PHST- 2018/06/09 06:00 [medline] PHST- 2017/11/01 00:00 [pmc-release] AID - ijms18112275 [pii] AID - ijms-18-02275 [pii] AID - 10.3390/ijms18112275 [doi] PST - epublish SO - Int J Mol Sci. 2017 Oct 30;18(11):2275. doi: 10.3390/ijms18112275.