Luteolin and Apigenin Attenuate LPS-Induced Astrocyte Activation and Cytokine Production by Targeting MAPK, STAT3, and N
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ORIGINAL ARTICLE
Luteolin and Apigenin Attenuate LPS-Induced Astrocyte Activation and Cytokine Production by Targeting MAPK, STAT3, and NF-κB Signaling Pathways Denis Nchang Che,1,2 Byoung Ok Cho,1 Ji-su Kim,1 Jae Young Shin,1 Hyun Ju Kang,1 and Seon Il Jang 1,3
Astrocytes release biologically active substances that cause inflammation in neurodegenerative diseases. The present study investigated the effects of two flavonoids (apigenin and luteolin) on the production of IL-31 and IL-33 in lipopolysaccharide (LPS)activated astrocytes. Cell viability was investigated using EZ-Cytox assay, mRNA expressions of IL-31 and IL-33 were analyzed by RT-PCR, protein expressions were analyzed by western blot, and cytokine secretion was analyzed by ELISA. Apigenin and luteolin prevented astrocyte activation and inhibited mRNA and protein expression and secretion of IL31 and IL-33 in the LPS-treated astrocytes. Apigenin’s suppression of ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 and IL-33, while luteolin’s suppression of JNK, p38, ERK, NF-κB, and STAT3 activations was responsible for the inhibition of IL-31 in the astrocytes. Also, luteolin’s suppression of ERK, NF-κB, and STAT3 activations inhibited IL-33 production in the activated astrocytes. In addition, apigenin and luteolin also prevented the translocation of activated STAT3 and NF-κB to the nucleus of the activated astrocytes and subsequently affected their DNA binding activities. The results suggest that apigenin and luteolin may have potentials as neuroprotective agents for the treatment of diseases involving astrocyte activation and detrimental production of IL31 and IL-33.
Abstract—
KEY WORDS: IL-31; IL-33; astrocytes; neuro-inflammation; lipopolysaccharides.
INTRODUCTION 1
Department of Health Management, Jeonju University, 303 Cheonjamro, Wansan-gu, Jeonju-si, Jeollabuk-do 55069, South Korea 2 Department of Food Science and Technology, Jeonbuk National University, Jeonju-si, Jeollabuk-do 54896, South Korea 3 To whom correspondence should be addressed at Department of Health Management, Jeonju University, 303 Cheonjam-ro, Wansan-gu, Jeonjusi, Jeollabuk-do 55069, South Korea. E-mail: [email protected]
Astrocytes constitute the most abundant cell population in the central nervous system (CNS) [1]. Like other cells of the CNS, astrocytes can release several biologically active substances capable of stimulating other cells [1, 2]. Under inflammatory conditions, astrocytes are said to be activated to produce pro-
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Che, Cho, Kim, Shin, Kang, and Jang inflammatory mediators like TNF-α and IL-1β [3]. In neurological diseases such as multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and HIV-1associated dementia (HAD), activated astrocytes activate NF-κB and STAT3 pathways to release proinflammatory cytokines and chemokines that induce cellular damage in the brain [4, 5]. Recently, astrocytes have been said to be new players in chr
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