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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Inhibition of MAPK and STAT3-SOCS3 by Sakuranetin Attenuated Chronic Allergic Airway Inflammation in Mice

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Santana, Fernanda P. R. [1, 2] ; da Silva, Rafael C. [1, 3] ; Grecco, Simone dos S. [4] ; Pinheiro, Aruana J. M. C. R. [5, 6] ; Caperuto, Luciana C. [1] ; Arantes-Costa, Fernanda M. [2] ; Claudio, Samuel R. [3] ; Yoshizaki, Kelly [7] ; Macchione, Mariangela [7] ; Ribeiro, Daniel A. [3] ; Tiberio, Iolanda F. L. C. ; Lima-Neto, Lidio G. [5, 6] ; Lago, Joao H. G. [8] ; Prado, Carla M. [1, 3, 2]
Total Authors: 14
[1] Univ Fed Sao Paulo, Dept Biol Sci, Diadema, SP - Brazil
[2] Univ Sao Paulo, Sch Med, Dept Med, Sao Paulo, SP - Brazil
[3] Univ Fed Sao Paulo, Dept Biosci, Santos - Brazil
[4] Univ Anhanguera Sao Paulo, Sao Paulo, SP - Brazil
[5] Univ CEUMA, Sao Luis, MA - Brazil
[6] Programa Posgrad Rede BIONORTE, Rio Branco - Brazil
[7] Univ Sao Paulo, Sch Med, Dept Pathol, Sao Paulo, SP - Brazil
[8] Fed Univ ABC, Ctr Nat Sci & Humanities, Santo Andre, SP - Brazil
Total Affiliations: 8
Document type: Journal article
Source: Mediators of Inflammation; v. 2019, SEP 3 2019.
Web of Science Citations: 0

Asthma allergic disease is caused by airway chronic inflammation. Some intracellular signaling pathways, such as MAPK and STAT3-SOCS3, are involved in the control of airway inflammation in asthma. The flavonoid sakuranetin demonstrated an anti-inflammatory effect in different asthma models. Our aim was to clarify how sakuranetin treatment affects MAPK and STAT3-SOCS3 pathways in a murine experimental asthma model. Mice were submitted to an asthma ovalbumin-induction protocol and were treated with vehicle, sakuranetin, or dexamethasone. We assayed the inflammatory profile, mucus production, and serum antibody, STAT3-SOCS3, and MAPK levels in the lungs. Morphological alterations were also evaluated in the liver. LPS-stimulated RAW 264.7 cells were used to evaluate the effects of sakuranetin on nitric oxide (NO) and cytokine production. In vivo, sakuranetin treatment reduced serum IgE levels, lung inflammation (eosinophils, neutrophils, and Th2/Th17 cytokines), and respiratory epithelial mucus production in ovalbumin-sensitized animals. Considering possible mechanisms, sakuranetin inhibits the activation of ERK1/2, JNK, p38, and STAT3 in the lungs. No alterations were found in the liver for treated animals. Sakuranetin did not modify in vitro cell viability in RAW 264.7 and reduced NO release and gene expression of IL-1 beta and IL-6 induced by LPS in these cells. In conclusion, our data showed that the inhibitory effects of sakuranetin on eosinophilic lung inflammation can be due to the inhibition of Th2 and Th17 cytokines and the inhibition of MAPK and STAT3 pathways, reinforcing the idea that sakuranetin can be considered a relevant candidate for the treatment of inflammatory allergic airway disease. (AU)

FAPESP's process: 18/06088-0 - Effects of eugenol and dehidrodieugenol isolated from Nectandra leucantha (Lauraceae) treatments in experimental models of acute and chronic lung disease
Grantee:Carla Máximo Prado
Support type: Regular Research Grants
FAPESP's process: 14/25689-4 - Effects of cholinergic system in acute and chronic pulmonary inflammation
Grantee:Carla Máximo Prado
Support type: Regular Research Grants