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Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release

Fibroblasts of different origins are known to possess stromal memory after inflammatory episodes. However, there are no studies exploring human lung fibroblast memory which may predict a subsequent inflammatory response in chronic respiratory diseases and COVID-19. MRC-5 and HF19 human lung fibrobla...

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Autores principales: Yap, Jennifer Maries Go, Ueda, Takashi, Kanemitsu, Yoshihiro, Takeda, Norihisa, Fukumitsu, Kensuke, Fukuda, Satoshi, Uemura, Takehiro, Tajiri, Tomoko, Ohkubo, Hirotsugu, Maeno, Ken, Ito, Yutaka, Oguri, Testsuya, Ugawa, Shinya, Niimi, Akio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356221/
https://www.ncbi.nlm.nih.gov/pubmed/35941890
http://dx.doi.org/10.3389/fimmu.2022.921728
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author Yap, Jennifer Maries Go
Ueda, Takashi
Kanemitsu, Yoshihiro
Takeda, Norihisa
Fukumitsu, Kensuke
Fukuda, Satoshi
Uemura, Takehiro
Tajiri, Tomoko
Ohkubo, Hirotsugu
Maeno, Ken
Ito, Yutaka
Oguri, Testsuya
Ugawa, Shinya
Niimi, Akio
author_facet Yap, Jennifer Maries Go
Ueda, Takashi
Kanemitsu, Yoshihiro
Takeda, Norihisa
Fukumitsu, Kensuke
Fukuda, Satoshi
Uemura, Takehiro
Tajiri, Tomoko
Ohkubo, Hirotsugu
Maeno, Ken
Ito, Yutaka
Oguri, Testsuya
Ugawa, Shinya
Niimi, Akio
author_sort Yap, Jennifer Maries Go
collection PubMed
description Fibroblasts of different origins are known to possess stromal memory after inflammatory episodes. However, there are no studies exploring human lung fibroblast memory which may predict a subsequent inflammatory response in chronic respiratory diseases and COVID-19. MRC-5 and HF19 human lung fibroblast cell lines were treated using different primary and secondary stimulus combinations: TNFα–WD–TNFα, Poly (I:C)–WD–TNFα, TNFα–WD–Poly (I:C), or LPS–WD–TNFα with a 24-h rest period (withdrawal period; WD) between the two 24-h stimulations. TLR3 and NF-κB inhibitors were used to determine pathways involved. The effect of SARS-Cov-2 spike protein to inflammatory response of lung fibroblasts was also investigated. mRNA expressions of genes and IL6 release were measured using qRT-PCR and ELISA, respectively. Statistical significance was determined by using one- or two-way ANOVA, followed by Bonferroni’s post hoc analysis for comparison of multiple groups. Preexposure with Poly (I:C) significantly increased TNFα-induced IL6 gene expression and IL6 release in both cell lines, while it affected neither gene expressions of IL1B, IL2, IL8, and MMP8 nor fibrosis-related genes: ACTA2, COL1A1, POSTN, and TGFB1. Inhibition of TLR3 or NF-κB during primary stimulation significantly downregulated IL6 release. Simultaneous treatment of MRC-5 cells with SARS-CoV-2 spike protein further increased TNFα-induced IL6 release; however, preexposure to Poly (I:C) did not affect it. Human lung fibroblasts are capable of retaining inflammatory memory and showed an augmented response upon secondary exposure. These results may contribute to the possibility of training human lung fibroblasts to respond suitably on inflammatory episodes after viral infection.
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spelling pubmed-93562212022-08-07 Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release Yap, Jennifer Maries Go Ueda, Takashi Kanemitsu, Yoshihiro Takeda, Norihisa Fukumitsu, Kensuke Fukuda, Satoshi Uemura, Takehiro Tajiri, Tomoko Ohkubo, Hirotsugu Maeno, Ken Ito, Yutaka Oguri, Testsuya Ugawa, Shinya Niimi, Akio Front Immunol Immunology Fibroblasts of different origins are known to possess stromal memory after inflammatory episodes. However, there are no studies exploring human lung fibroblast memory which may predict a subsequent inflammatory response in chronic respiratory diseases and COVID-19. MRC-5 and HF19 human lung fibroblast cell lines were treated using different primary and secondary stimulus combinations: TNFα–WD–TNFα, Poly (I:C)–WD–TNFα, TNFα–WD–Poly (I:C), or LPS–WD–TNFα with a 24-h rest period (withdrawal period; WD) between the two 24-h stimulations. TLR3 and NF-κB inhibitors were used to determine pathways involved. The effect of SARS-Cov-2 spike protein to inflammatory response of lung fibroblasts was also investigated. mRNA expressions of genes and IL6 release were measured using qRT-PCR and ELISA, respectively. Statistical significance was determined by using one- or two-way ANOVA, followed by Bonferroni’s post hoc analysis for comparison of multiple groups. Preexposure with Poly (I:C) significantly increased TNFα-induced IL6 gene expression and IL6 release in both cell lines, while it affected neither gene expressions of IL1B, IL2, IL8, and MMP8 nor fibrosis-related genes: ACTA2, COL1A1, POSTN, and TGFB1. Inhibition of TLR3 or NF-κB during primary stimulation significantly downregulated IL6 release. Simultaneous treatment of MRC-5 cells with SARS-CoV-2 spike protein further increased TNFα-induced IL6 release; however, preexposure to Poly (I:C) did not affect it. Human lung fibroblasts are capable of retaining inflammatory memory and showed an augmented response upon secondary exposure. These results may contribute to the possibility of training human lung fibroblasts to respond suitably on inflammatory episodes after viral infection. Frontiers Media S.A. 2022-07-22 /pmc/articles/PMC9356221/ /pubmed/35941890 http://dx.doi.org/10.3389/fimmu.2022.921728 Text en Copyright © 2022 Yap, Ueda, Kanemitsu, Takeda, Fukumitsu, Fukuda, Uemura, Tajiri, Ohkubo, Maeno, Ito, Oguri, Ugawa and Niimi https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
Yap, Jennifer Maries Go
Ueda, Takashi
Kanemitsu, Yoshihiro
Takeda, Norihisa
Fukumitsu, Kensuke
Fukuda, Satoshi
Uemura, Takehiro
Tajiri, Tomoko
Ohkubo, Hirotsugu
Maeno, Ken
Ito, Yutaka
Oguri, Testsuya
Ugawa, Shinya
Niimi, Akio
Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release
title Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release
title_full Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release
title_fullStr Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release
title_full_unstemmed Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release
title_short Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release
title_sort human lung fibroblasts exhibit induced inflammation memory via increased il6 gene expression and release
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356221/
https://www.ncbi.nlm.nih.gov/pubmed/35941890
http://dx.doi.org/10.3389/fimmu.2022.921728
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