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Quercetin inhibits the poly(dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed human keratinocytes.
Biochem Biophys Res Commun 2018; 503(1):116-122BB

Abstract

Quercetin, a polyphenol, belongs to a class of flavonoids that exerts anti-inflammatory effects. Interleukin (IL)-18 is a member of the IL-1 family cytokine that regulates immune responses and is implicated in various inflammatory skin diseases. Absent in melanoma 2 (AIM2) is a cytosolic double-stranded (ds) DNA sensor that recognizes the dsDNA of a microbial or host origin. Binding of dsDNA to AIM2 simulates caspase-1-dependent inflammasome activity, which leads to the production of IL-1β and IL-18. Increased levels of AIM2 have been observed in patients with inflammatory skin diseases. In the current study, we investigated the issue of whether or how Quercetin attenuates poly (dA:dT), a synthetic analog of microbial dsDNA, -induced IL-18 secretion in IFN-γ-primed human keratinocytes. Treatment with 5 and 10 μM of Quercetin inhibited the poly (dA:dT)-induced secretion of IL-18 after IFN-γ priming and before poly (dA:dT)-induced AIM2 activation. In addition, treatment with Quercetin at 10 μM, significantly inhibited the phosphorylation of JAK2 and STAT1, and the nuclear translocation of phosphorylated STAT1 in poly (dA:dT)-treated and IFN-γ-primed keratinocytes. These results suggest that treatment with Quercetin inhibits the poly (dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed keratinocytes.

Authors+Show Affiliations

Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea.Institute of Hansen's Disease, Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, South Korea. Electronic address: sebelee1@gmail.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29857000

Citation

Lee, Kyung-Mi, et al. "Quercetin Inhibits the poly(dA:dT)-induced Secretion of IL-18 Via Down-regulation of the Expressions of AIM2 and Pro-caspase-1 By Inhibiting the JAK2/STAT1 Pathway in IFN-γ-primed Human Keratinocytes." Biochemical and Biophysical Research Communications, vol. 503, no. 1, 2018, pp. 116-122.
Lee KM, Kang JH, Yun M, et al. Quercetin inhibits the poly(dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed human keratinocytes. Biochem Biophys Res Commun. 2018;503(1):116-122.
Lee, K. M., Kang, J. H., Yun, M., & Lee, S. B. (2018). Quercetin inhibits the poly(dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed human keratinocytes. Biochemical and Biophysical Research Communications, 503(1), pp. 116-122. doi:10.1016/j.bbrc.2018.05.191.
Lee KM, et al. Quercetin Inhibits the poly(dA:dT)-induced Secretion of IL-18 Via Down-regulation of the Expressions of AIM2 and Pro-caspase-1 By Inhibiting the JAK2/STAT1 Pathway in IFN-γ-primed Human Keratinocytes. Biochem Biophys Res Commun. 2018 09 3;503(1):116-122. PubMed PMID: 29857000.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quercetin inhibits the poly(dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed human keratinocytes. AU - Lee,Kyung-Mi, AU - Kang,Jung Hoon, AU - Yun,Mihee, AU - Lee,Seong-Beom, Y1 - 2018/06/06/ PY - 2018/05/23/received PY - 2018/05/28/accepted PY - 2018/6/2/pubmed PY - 2018/11/27/medline PY - 2018/6/2/entrez KW - AIM (absent in melanoma) 2 KW - IL (interleukin)-18 KW - Inflammasome KW - JAK/STAT pathway KW - Keratinocytes KW - Quercetin SP - 116 EP - 122 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 503 IS - 1 N2 - Quercetin, a polyphenol, belongs to a class of flavonoids that exerts anti-inflammatory effects. Interleukin (IL)-18 is a member of the IL-1 family cytokine that regulates immune responses and is implicated in various inflammatory skin diseases. Absent in melanoma 2 (AIM2) is a cytosolic double-stranded (ds) DNA sensor that recognizes the dsDNA of a microbial or host origin. Binding of dsDNA to AIM2 simulates caspase-1-dependent inflammasome activity, which leads to the production of IL-1β and IL-18. Increased levels of AIM2 have been observed in patients with inflammatory skin diseases. In the current study, we investigated the issue of whether or how Quercetin attenuates poly (dA:dT), a synthetic analog of microbial dsDNA, -induced IL-18 secretion in IFN-γ-primed human keratinocytes. Treatment with 5 and 10 μM of Quercetin inhibited the poly (dA:dT)-induced secretion of IL-18 after IFN-γ priming and before poly (dA:dT)-induced AIM2 activation. In addition, treatment with Quercetin at 10 μM, significantly inhibited the phosphorylation of JAK2 and STAT1, and the nuclear translocation of phosphorylated STAT1 in poly (dA:dT)-treated and IFN-γ-primed keratinocytes. These results suggest that treatment with Quercetin inhibits the poly (dA:dT)-induced secretion of IL-18 via down-regulation of the expressions of AIM2 and pro-caspase-1 by inhibiting the JAK2/STAT1 pathway in IFN-γ-primed keratinocytes. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/29857000/Quercetin_inhibits_the_poly_dA:dT__induced_secretion_of_IL_18_via_down_regulation_of_the_expressions_of_AIM2_and_pro_caspase_1_by_inhibiting_the_JAK2/STAT1_pathway_in_IFN_γ_primed_human_keratinocytes_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(18)31280-4 DB - PRIME DP - Unbound Medicine ER -