PMID- 31593984 OWN - NLM STAT- MEDLINE DCOM- 20200127 LR - 20200127 IS - 1552-5783 (Electronic) IS - 0146-0404 (Linking) VI - 60 IP - 13 DP - 2019 Oct 1 TI - Therapeutic Effect of Curcumin, a Plant Polyphenol Extracted From Curcuma longae, in Fibroblasts From Patients With Graves' Orbitopathy. PG - 4129-4140 LID - 10.1167/iovs.19-27376 [doi] AB - PURPOSE: We examined the therapeutic effect of nontoxic concentrations of curcumin, a plant polyphenol extracted from Curcuma longae, in primary cultures of orbital fibroblasts from Graves' orbitopathy (GO). METHODS: The effect of curcumin on interleukin (IL)-1beta induced-proinflammatory cytokine production was determined using quantitative real-time PCR, enzyme-linked immunosorbent assay (ELISA), and Western blot analysis. Adipogenic differentiation was identified using Oil-Red O staining, and levels of peroxisome proliferator activator gamma (PPARgamma) and CCAAT-enhancer-binding proteins (C/EBP) alpha/beta were determined by Western blot analyses. Antioxidant activity was measured using an oxidant-sensitive fluorescent probe to detect intracellular reactive oxygen species (ROS) generated in response to hydrogen peroxide (H2O2) and cigarette smoke extract (CSE). RESULTS: Treatment with curcumin resulted in a dose- and time-dependent decrease in IL-1beta-induced synthesis of inflammatory cytokines, including IL-6, IL-8, MCP-1, and ICAM-1 at both mRNA and protein levels. Decrease in lipid droplets and expression of PPARgamma and c/EBPalpha/beta were noted in fibroblasts treated with curcumin during adipose differentiation. CSE- or H2O2-induced ROS synthesis was significantly lower in curcumin-treated fibroblasts in comparison with the control. Curcumin significantly suppressed IL-1beta-induced phosphorylated extracellular signal-regulated kinase, Akt, c-Jun NH(2)-terminal kinase, and nuclear factor kappa-light-chain-enhancer of activated B cells, p65 proteins and stimulated beta-catenin translocation into nucleus during adipogenesis. CONCLUSIONS: Curcumin inhibits proinflammatory cytokine production, ROS synthesis, and adipogenesis in orbital fibroblasts of GO patients in vitro possibly related to multiple proinflammatory signaling molecules and beta-catenin pathway. The results of the study support potential use of the curcumin in the treatment of GO. FAU - Lee, Jihei Sara AU - Lee JS AD - Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea. FAU - Kim, Jinjoo AU - Kim J AD - Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea. FAU - Lee, Eun Jig AU - Lee EJ AD - Department of Endocrinology, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. FAU - Yoon, Jin Sook AU - Yoon JS AD - Department of Ophthalmology, Severance Hospital, Institute of Vision Research, Yonsei University College of Medicine, Seoul, Korea. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Cytokines) RN - 0 (Plant Extracts) RN - IT942ZTH98 (Curcumin) SB - IM MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Curcumin/*pharmacology MH - Cytokines/metabolism MH - Fibroblasts/*drug effects/metabolism MH - Graves Ophthalmopathy/*drug therapy/metabolism MH - Humans MH - Oxidative Stress/drug effects MH - Plant Extracts/*pharmacology EDAT- 2019/10/09 06:00 MHDA- 2020/01/28 06:00 CRDT- 2019/10/09 06:00 PHST- 2019/10/09 06:00 [entrez] PHST- 2019/10/09 06:00 [pubmed] PHST- 2020/01/28 06:00 [medline] AID - 2752497 [pii] AID - 10.1167/iovs.19-27376 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2019 Oct 1;60(13):4129-4140. doi: 10.1167/iovs.19-27376.