FGF-21 Elevated IL-10 Production to Correct LPS-Induced Inflammation
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ORIGINAL ARTICLE
FGF-21 Elevated IL-10 Production to Correct LPS-Induced Inflammation Jun-yan Li,1 Nan Wang,1 Mir Hassan Khoso,1 Cheng-bin Shen,1 Meng-ze Guo,1 Xin-xin Pang,1 De-shan Li,1,3 and Wen-fei Wang2,3
Fibroblast growth factor 21 (FGF-21) has been previously judged as a major metabolic regulator. In this paper, we show that FGF-21 has a potential role in antiinflammation and immunoregulation. In vivo, treatment with exogenous FGF-21 can alleviate LPS-induced inflammation. In vitro, FGF-21 inhibited LPS-induced IL-1β expression in THP-1 cells. Furthermore, besides the NF-κB pathway, the mechanism of action of FGF-21 was observed to involve the elevation of IL-10 in the ERK1/2 pathway. This study clearly indicates that FGF21 can be used as an attractive target for the management of inflammatory disorders. This piece of research indicates that FGF-21 could have much value in the management of inflammatory disorders.
Abstract—
KEY WORDS: FGF-21; THP-1 cells; IL-10; LPS.
Sepsis, when induced by bacterial infection, has a continuum beginning with a host-pathogen interaction that activates a complex interplay between pro-inflammatory and anti-inflammatory states [1]. At the start of inflammation, the monocytes/macrophages and other inflammatory cells are activated to undergo migration, proliferation, phagocytosis, and secrete endogenous or exogenous substances to defend against infection. However, this beneficial response will become harmful when it is out of control. The overproduction of interleukin-1 IL-1β (IL-1 IL-1β) and other proinflammatory cytokines leads to a pro-inflammation/anti-inflammation response imbalance. If this situation is not 1
Northeast Agricultural University, School of Life Science, Harbin, Heilongjiang Province, China 2 Life Science and Biotechnique Research Center, A Division of Northeast Agricultural University, Harbin, Heilongjiang Province 150030, China 3 To whom correspondence should be addressed to Wen-fei Wang at Life Science and Biotechnique Research Center, A Division of Northeast Agricultural University, Harbin, Heilongjiang Province 150030, China. E-mail: [email protected]; and De-shan Li at Northeast Agricultural University, School of Life Science, Harbin, Heilongjiang Province, China. E-mail: [email protected]
corrected immediately, the following cascade effect may lead to systemic inflammatory response syndrome (SIRS) or multiple organ dysfunction syndrome (MODS) or even death. In fact, the incidence of cases in which sepsis and severe sepsis lead to as a major common pathway for end-of-life events has increased considerably in the past few decades and is expected to increase further [2, 3]. Fibroblast growth factor-21 (FGF-21), a cytokine which is mainly produced by the liver, has been identified as an important metabolic regulator of glucose and lipids in vertebrates [4–7]. Though some studies indicate that serum C-reactive protein levels, IL-6, TNF-α, and leptin mRNA levels in white adipocytes have been reduced by the administration of FGF-21 [5–8], these benef
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