Fibroblast growth factor 21 (FGF21) inhibits macrophage-mediated inflammation by activating Nrf2 and suppressing the NF-κB signaling pathway.
Our previous report has shown that FGF21 has anti-inflammatory properties in a collagen-induced arthritis (CIA) model. In this study, the underlying molecular mechanisms of action were also investigated using RAW 264.7 cells, a murine monocyte-macrophage. RAW 264.7 cells were pre-incubated with various concentrations (2000, 500, 100ng/ml) of FGF21 and stimulated with LPS to induce oxidative stress and inflammation. The result of flow cytometry showed that β-Klotho, FGF21 specific receptor, was expressed in murine splenic macrophages and RAW 264.7. In vitro, FGF21 reduced the expression of TNF-α, IL-1β, IL-6 and IFN-γ and increased the level of IL-10 in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophages. FGF21 also suppressed profound elevation of ROS production and oxidative stress, as evidenced by an increase of the MDA level and depletion of the intracellular GSH level, and restored the activities of antioxidant enzymes SOD and GSH-Px in LPS-stimulated RAW 264.7 macrophages. Moreover, FGF21 inhibited LPS-induced nuclear factor-κB (NF-κB) activation, including degradation of I-κB and nuclear translocation of p65. In addition, the result of Western blot and real-time PCR showed that FGF21 induced heme oxygenase-1 (HO-1) expression and increased the nuclear transcription factor-E2-related factor 2 (Nrf2) levels in a dose-dependent manner in LPS-stimulated RAW 264.7 macrophages. In conclusion, the results suggest that macrophages are the targets for the anti-inflammatory effects of FGF21, and FGF21 exerted an anti-inflammatory effect mainly via enhancing Nrf2-mediated anti-oxidant capacity and suppressing NF-κB signaling pathway.
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Harbin Pacific Biopharmaceutical Co., Ltd, Harbin 150030, China.
Yinhang
Y
Yu
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
Jinjiao
J
He
Harbin University of Commerce, Harbin 150028, China.
Siming
S
Li
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
Liying
L
Song
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
Xiaochen
X
Guo
BD Biosciences Department, Becton Dickinson Medical Devices (Shanghai) Co Ltd., 9, 10/F, Tower 3, JingAn Kerry Center, 1128 Yan'an Road (M), Shanghai 200040, China.
Wenbing
W
Yao
Heilongjiang Bayi Agricultural University, 163319, China.
Dehua
D
Zou
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
Xinyu
X
Gao
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
Yunye
Y
Liu
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China.
Fuliang
F
Bai
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Functional Gene, Harbin 150030, China.
Guiping
G
Ren
Bio-pharmaceutical Lab, Life Science College, Northeast Agricultural University, Harbin 150030, China; Key Laboratory of Agricultural Biological Functional Gene, Harbin 150030, China. Electronic address: deshanli@163.com.
Deshan
D
Li
D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000276:immunology / Q000378:metabolism*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007249:Inflammation; D000090265:Klotho Proteins; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress; D000067996:RAW 264.7 Cells; D015398:Signal Transduction
D016207:Cytokines; C418622:Klb protein, mouse; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D016328:NF-kappa B; C495636:Nfe2l2 protein, mouse; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; D051547:Heme Oxygenase-1; D000090265:Klotho Proteins
FGF21; LPS; NF-κB; Nrf2-mediated anti-oxidant capacity; RAW264.7 macrophages