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DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells

Interleukin-1β (IL-1β) is a prominent pro-inflammatory cytokine that is implicated in a variety of autoimmune diseases and plays an important role in host defense against infections. IL-1β activity increases with its increasing binding capacity to IL-1 receptors (IL-1Rs). Thus, numerous studies have...

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Autores principales: Ahn, Sun-Hee, Lee, Jin-Kyung, Kim, Nam Doo, Kim, Seok-Ho, Lee, Sunwoo, Jung, Seunggon, Chay, Kee-Oh, Lee, Tae-Hoon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073580/
https://www.ncbi.nlm.nih.gov/pubmed/29932110
http://dx.doi.org/10.3390/ijms19071835
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author Ahn, Sun-Hee
Lee, Jin-Kyung
Kim, Nam Doo
Kim, Seok-Ho
Lee, Sunwoo
Jung, Seunggon
Chay, Kee-Oh
Lee, Tae-Hoon
author_facet Ahn, Sun-Hee
Lee, Jin-Kyung
Kim, Nam Doo
Kim, Seok-Ho
Lee, Sunwoo
Jung, Seunggon
Chay, Kee-Oh
Lee, Tae-Hoon
author_sort Ahn, Sun-Hee
collection PubMed
description Interleukin-1β (IL-1β) is a prominent pro-inflammatory cytokine that is implicated in a variety of autoimmune diseases and plays an important role in host defense against infections. IL-1β activity increases with its increasing binding capacity to IL-1 receptors (IL-1Rs). Thus, numerous studies have targeted the discovery of molecules modulating the interactions between IL-1β and IL-1R1. We have conducted an IL-1R1 structure-based virtual screening to identify small molecules that could alter IL-1β activity, using in silico computational analysis. Sixty compounds from commercial libraries were predicted to bind to IL-1R1, and their influence on cytokine production in IL-1β-stimulated gingival fibroblasts (GFs) was determined. Of these, only (2-(1,2-diphenyl-1H-indol-3-yl)ethanamine (DPIE) showed a synergistic increase in inflammatory molecules and cytokine production (IL-6, IL-8, and COX-2) at both mRNA and protein levels in IL-1β-stimulated GFs. The enhancing activity of DPIE in IL-1β-induced cytokine production increased in a dose-dependent manner without cytotoxicity. This pattern was also observed in IL-1β-stimulated primary human periodontal ligament cells (PDLs). Furthermore, we measured the impact of DPIE on the IL-1β–IL-1R1 system using surface plasmon resonance and demonstrated that DPIE increased the binding affinity of IL-1β to IL-1R1. These data indicate that DPIE boosts IL-1β signaling by enhancing the binding of IL-1β to IL-1R1 in oral primary cells.
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spelling pubmed-60735802018-08-13 DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells Ahn, Sun-Hee Lee, Jin-Kyung Kim, Nam Doo Kim, Seok-Ho Lee, Sunwoo Jung, Seunggon Chay, Kee-Oh Lee, Tae-Hoon Int J Mol Sci Article Interleukin-1β (IL-1β) is a prominent pro-inflammatory cytokine that is implicated in a variety of autoimmune diseases and plays an important role in host defense against infections. IL-1β activity increases with its increasing binding capacity to IL-1 receptors (IL-1Rs). Thus, numerous studies have targeted the discovery of molecules modulating the interactions between IL-1β and IL-1R1. We have conducted an IL-1R1 structure-based virtual screening to identify small molecules that could alter IL-1β activity, using in silico computational analysis. Sixty compounds from commercial libraries were predicted to bind to IL-1R1, and their influence on cytokine production in IL-1β-stimulated gingival fibroblasts (GFs) was determined. Of these, only (2-(1,2-diphenyl-1H-indol-3-yl)ethanamine (DPIE) showed a synergistic increase in inflammatory molecules and cytokine production (IL-6, IL-8, and COX-2) at both mRNA and protein levels in IL-1β-stimulated GFs. The enhancing activity of DPIE in IL-1β-induced cytokine production increased in a dose-dependent manner without cytotoxicity. This pattern was also observed in IL-1β-stimulated primary human periodontal ligament cells (PDLs). Furthermore, we measured the impact of DPIE on the IL-1β–IL-1R1 system using surface plasmon resonance and demonstrated that DPIE increased the binding affinity of IL-1β to IL-1R1. These data indicate that DPIE boosts IL-1β signaling by enhancing the binding of IL-1β to IL-1R1 in oral primary cells. MDPI 2018-06-22 /pmc/articles/PMC6073580/ /pubmed/29932110 http://dx.doi.org/10.3390/ijms19071835 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ahn, Sun-Hee
Lee, Jin-Kyung
Kim, Nam Doo
Kim, Seok-Ho
Lee, Sunwoo
Jung, Seunggon
Chay, Kee-Oh
Lee, Tae-Hoon
DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells
title DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells
title_full DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells
title_fullStr DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells
title_full_unstemmed DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells
title_short DPIE [2-(1,2-diphenyl-1H-indol-3-yl)ethanamine] Augments Pro-Inflammatory Cytokine Production in IL-1β-Stimulated Primary Human Oral Cells
title_sort dpie [2-(1,2-diphenyl-1h-indol-3-yl)ethanamine] augments pro-inflammatory cytokine production in il-1β-stimulated primary human oral cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6073580/
https://www.ncbi.nlm.nih.gov/pubmed/29932110
http://dx.doi.org/10.3390/ijms19071835
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