RRC ID 73167
Author Yap JMG, Ueda T, Kanemitsu Y, Takeda N, Fukumitsu K, Fukuda S, Uemura T, Tajiri T, Ohkubo H, Maeno K, Ito Y, Oguri T, Ugawa S, Niimi A.
Title Human Lung Fibroblasts Exhibit Induced Inflammation Memory via Increased IL6 Gene Expression and Release.
Journal Front Immunol
Abstract 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.
Volume 13
Pages 921728
Published 2022-1-1
DOI 10.3389/fimmu.2022.921728
PMID 35941890
PMC PMC9356221
MeSH COVID-19* Fibroblasts / metabolism Gene Expression Humans Inflammation / chemically induced Inflammation / genetics Inflammation / metabolism Interleukin-6 / genetics* Interleukin-6 / metabolism Lung / metabolism NF-kappa B / metabolism Poly I-C / metabolism Poly I-C / pharmacology SARS-CoV-2 Spike Glycoprotein, Coronavirus Toll-Like Receptor 3 / genetics Toll-Like Receptor 3 / metabolism Tumor Necrosis Factor-alpha* / metabolism
IF 5.085
Human and Animal Cells MRC-5(RCB0218) HF19(RCB0210)