Resveratrol increases the activation markers and changes the release of inflammatory cytokines of hepatic stellate cells
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Resveratrol increases the activation markers and changes the release of inflammatory cytokines of hepatic stellate cells Cleverson Moraes de Oliveira1 · Leo Anderson Meira Martins1,2 · Arieli Cruz de Sousa1 · Ketlen da Silveira Moraes1 · Bruna Pasqualotto Costa3 · Moema Queiroz Vieira1 · Bárbara Paranhos Coelho1 · Radovan Borojevic4 · Jarbas Rodrigues de Oliveira3 · Fátima Costa Rodrigues Guma1,5 Received: 26 June 2020 / Accepted: 7 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The phytoalexin Resveratrol (3,5,4′-trihydroxystilbene; RSV) has been related to numerous beneficial effects on health by its cytoprotection and chemoprevention activities. Liver fibrosis is characterized by the extracellular matrix accumulation after hepatic injury and can lead to cirrhosis. Hepatic stellate cells (HSC) play a crucial role during fibrogenesis and liver wound healing by changing their quiescent phenotype to an activated phenotype for protecting healthy areas from damaged areas. Strategies on promoting the activated HSC death, the quiescence return or the cellular activation stimuli decrease play an important role on reducing liver fibrosis. Here, we evaluated the RSV effects on some markers of activation in GRX, an HSC model. We further evaluated the RSV influence in the ability of GRX on releasing inflammatory mediators. RSV at 1 and 10 µM did not alter the protein content of α-SMA, collagen I and GFAP; but 50 µM increased the content of these activation-related proteins. Also, RSV did not change the myofibroblast-like morphology of GRX. Interestingly, RSV at 10 and 50 µM decreased the GRX migration and collagen-I gel contraction. Finally, we showed that RSV triggered the increase in the TNF-α and IL-10 content in culture media of GRX while the opposite occurred for the IL-6 content. Altogether, these results suggested that RSV did not decrease the activation state of GRX and oppositely, triggered a pro-activation effect at the 50 µM concentration. However, despite the increase of TNF- α in culture media, these results on IL-6 and IL-10 secretion were in accordance with the anti-inflammatory role of RSV in our model. Keywords Hepatic stellate cells · Liver fibrosis · Liver wound healing · Resveratrol
Introduction * Cleverson Moraes de Oliveira [email protected] 1
Departmento de Bioquímica, ICBS, Universidade Federal Do Rio Grande Do Sul (UFRGS), Rua Ramiro Barcelos, 2600‑Anexo I, Porto Alegre, RS, CEP 90035‑003, Brazil
2
Departamento de Fisiologia, ICBS, Universidade Federal Do Rio Grande Do Sul, Rua Sarmento Leite, Porto Alegre, RS, CEP 500, Brazil
3
Laboratório de Pesquisa Em Biofísica Celular E Inflamação, Pontifícia Universidade Católica Do Rio Grande Do Sul (PUCRS), Porto Alegre, RS, Brazil
4
Centro de Medicina Regenerativa, Faculdade de Medicina de Petrópolis, Petrópolis, RJ, Brazil
5
Centro de Microscopia E Microanálise (CMM), Universidade Federal Do Rio Grande Do Sul, Av. Bento Gonçalves, 9500 ‑ Prédio 43.177 ‑ Bl 1Campus do Vale, Porto Alegre,
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