A Novel Role of PM Extracts on the Post-Transcriptional Control of Pro-Inflammatory Mediators, IL-6 and CXCL8

Evasomary Rivera-Ramírez,Andrea Ortíz-Rivera,Loyda B Méndez,Braulio Jiménez-Vélez,Rosa I Rodríguez-Cotto

doi:10.3390/atmos10050270

Abstract

Exposure to airborne particulate matter (PM) has been associated with the transcriptional up-regulation of pro-inflammatory mediators. However, the effect of PM on post-transcriptional regulation of pro-inflammatory mediators has not been fully explored. In this study, we examined the acute effect of organic extracts from urban PM, rural PM and diesel exhaust particles (DEP) on the post-transcriptional control of interleukin-6 (IL-6) and interleukin-8 (CXCL8) using a human bronchial epithelial cell line. Both PM and DEP extracts induced the release of IL-6 and CXCL8 after 24 h of exposure. Time-course experiments were conducted to examine changes in mRNA steady-state levels and half-lives. The steady-state levels of CXCL8 mRNA increase at 15 min on cells exposed to both PM and DEP extracts. Meanwhile only the urban extract induced significant increases of IL-6 mRNA levels at 15 min. Indirect measurements of IL-6 mRNA half-life showed a dramatic increase in cells exposed to the organic extracts. CXCL8 mRNA half-life increases in cells exposed to PM extracts and not DEP extract. Nuclear run-ons demonstrated that the urban PM and DEP extracts promoted an up-regulation in the transcription rate of CXCL8 at 15 min but not for IL-6. Urban and rural PM influences the post-transcriptional control of CXCL8.

Highlights

Epidemiological, clinical, in vivo and in vitro studies have shown consistent associations between airborne particulate matter (PM) exposure and adverse respiratory effects [1]
Since in this study we observed significant increases in the mRNA levels of IL-6 and CXCL8 mRNAs as early as 15 min, we evaluated whether the PM extracts had an effect in the post-transcriptional regulation of these pro-inflammatory mediators
The slight increase in steady-state CXCL8 mRNA at 60 min can be correlated to the cytoplasmic export of the de novo transcripts produced after 15 min of exposure. These results provide evidence that PM2.5 has a role in the post-transcriptional regulation of IL-6 and CXCL8

Summary

Introduction

Epidemiological, clinical, in vivo and in vitro studies have shown consistent associations between airborne particulate matter (PM) exposure and adverse respiratory effects [1]. In vitro studies have demonstrated that PM2.5 exposure can induce the production of pro-inflammatory cytokines and chemokines, such as interleukin-6 (IL-6) and interleukin-8 (CXCL8) [2,3,4,5,6,7,8,9,10,11,12]. Atmosphere 2019, 10, 270 mechanisms can regulate the fate of mRNAs in association with RNA-binding proteins allowing cells to respond rapidly to extracellular stimulus by inducing different signaling pathways that lengthens or shortens target mRNA half-lives and the abundance of functional proteins [14,15,17,18]. One of the most important post-transcriptional control mechanisms involved in the regulation of mRNA half-lives of pro-inflammatory mediators is the AU-rich elements-mediated decay pathway

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