title: Solanesol induces the expression of heme oxygenase-1 via p38 and Akt and suppresses the production of proinflammatory cytokines in RAW264.7 cells.
abstract: The aim of the present study was to examine the anti-inflammatory effect of solanesol and to elucidate the underlying mechanisms. Heme oxygenase-1 (HO-1) plays an important role in cytoprotection against oxidative stress and inflammation. Solanesol induced HO-1 expression both at the level of mRNA and proteins, resulting in increased HO-1 activity. Solanesol treatment enhanced the level of the phosphorylated form, nuclear translocation, ARE-binding, and transcriptional activity of Nrf2. p38 and Akt contributed to ARE-driven HO-1 expression. Solanesol activated both p38 and Akt, and treatments with SB203580 (a p38 kinase inhibitor), LY294002 (an Akt inhibitor), specific p38 siRNA and Akt siRNA suppressed the solanesol-induced activation of Nrf2, resulting in a decrease in HO-1 expression. Solanesol also elevated the autophagic protein LC3B-II level. SnPP (a HO-1 inhibitor) and HO-1 siRNA markedly abolished the anti-inflammatory effect of solanesol against LPS-induced cell damage. Likewise, SB203580, LY294002, 3-MA and Baf-A1 inhibited the solanesol-induced anti-inflammatory effect. These studies demonstrate that solanesol attenuates inflammation by HO-1 induction via p38 and Akt signaling. Thus, it is quite plausible that HO-1 induction by solanesol could trigger anti-inflammatory pathways including limiting LPS-stimulated cytokine production through autophagic signaling via p38 and Akt.
authors.affiliation: Department of Biology and Food Engineering, Bengbu University, Bengbu, PR China. leeyxy@163.com.
authors.forename: Xiangyang
authors.initials: X
authors.lastname: Yao
authors.affiliation: School of Pharmacy, Fudan University, Shanghai, PR China.
authors.forename: Binyu
authors.initials: B
authors.lastname: Lu
authors.affiliation: Department of Biology and Food Engineering, Bengbu University, Bengbu, PR China. leeyxy@163.com.
authors.forename: Chaotian
authors.initials: C
authors.lastname: Lü
authors.affiliation: Department of Biology and Food Engineering, Bengbu University, Bengbu, PR China. leeyxy@163.com.
authors.forename: Qin
authors.initials: Q
authors.lastname: Bai
authors.affiliation: School of Biology and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan, PR China.
authors.forename: Dazhong
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Biology and Food Engineering, Bengbu University, Bengbu, PR China. leeyxy@163.com.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Biology and Food Engineering, Bengbu University, Bengbu, PR China. leeyxy@163.com.
authors.forename: Zibing
authors.initials: Z
authors.lastname: Hong
authors.affiliation: Department of Biology and Food Engineering, Bengbu University, Bengbu, PR China. leeyxy@163.com.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016207:Cytokines / Q000235:genetics / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000276:immunology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000276:immunology*; D000067996:RAW 264.7 Cells; D013729:Terpenes / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000276:immunology*
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D013729:Terpenes; D051547:Heme Oxygenase-1; C514862:Akt1 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases; C017719:solanesol