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Type 1 interferon and pattern recognition receptor signaling following particulate matter inhalation

ABSTRACT: This study utilized microarray technology as an exploratory search for mechanisms of systemic effects after welding fume inhalation. In addition, the applicability of this methodological approach for determining specific exposure-induced responses was examined.

ORGANISM(S): Mus musculus

PROVIDER: GSE34056 | GEO | 2011/12/18

SECONDARY ACCESSION(S): PRJNA150023

REPOSITORIES: GEO

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Type 1 interferon and pattern recognition receptor signaling following particulate matter inhalation

Project description:This study utilized microarray technology as an exploratory search for mechanisms of systemic effects after welding fume inhalation. In addition, the applicability of this methodological approach for determining specific exposure-induced responses was examined. C57Bl/6J mice were exposed to gas metal arc-stainless steel (GMA-SS) welding fume by inhalation for 10 days (3 hours/day) at 40 mg/m3. Microarray analysis was done on lung, blood and aorta from n=4 mice exposed to welding fume or air (control).

2011-12-18 | E-GEOD-34056 | biostudies-arrayexpress

Type I interferon and pattern recognition receptor signaling following particulate matter inhalation.

Project description:BACKGROUND: Welding, a process that generates an aerosol containing gases and metal-rich particulates, induces adverse physiological effects including inflammation, immunosuppression and cardiovascular dysfunction. This study utilized microarray technology and subsequent pathway analysis as an exploratory search for markers/mechanisms of in vivo systemic effects following inhalation. Mice were exposed by inhalation to gas metal arc - stainless steel (GMA-SS) welding fume at 40?mg/m3 for 3?hr/d for 10?d and sacrificed 4?hr, 14?d and 28?d post-exposure. Whole blood cells, aorta and lung were harvested for global gene expression analysis with subsequent Ingenuity Pathway Analysis and confirmatory qRT-PCR. Serum was collected for protein profiling. RESULTS: The novel finding was a dominant type I interferon signaling network with the transcription factor Irf7 as a central component maintained through 28?d. Remarkably, these effects showed consistency across all tissues indicating a systemic type I interferon response that was complemented by changes in serum proteins (decreased MMP-9, CRP and increased VCAM1, oncostatin M, IP-10). In addition, pulmonary expression of interferon ? and ? and Irf7 specific pattern recognition receptors (PRR) and signaling molecules (Ddx58, Ifih1, Dhx58, ISGF3) were induced, an effect that showed specificity when compared to other inflammatory exposures. Also, a canonical pathway indicated a coordinated response of multiple PRR and associated signaling molecules (Tlr7, Tlr2, Clec7a, Nlrp3, Myd88) to inhalation of GMA-SS. CONCLUSION: This methodological approach has the potential to identify consistent, prominent and/or novel pathways and provides insight into mechanisms that contribute to pulmonary and systemic effects following toxicant exposure.

| S-EPMC3537608 | biostudies-literature

Tendon methylation microarray after particulate matter inhalation

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Acute effects of particulate matter (EHC-93) inhalation in mice with chronic lung inflammation

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Oxidative Stress and Reduced Responsiveness of Challenged Circulating Leukocytes Following Pulmonary Instillation of Metal-Rich Particulate Matter in Rats

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Tendon methylation microarray after particulate matter inhalation

Project description:Open tenotomy of the Achilles tendon of 6 rats was performed. The animals were divided into two groups according to exposure of PM2.5 (particulate matter less than 2.5 µm): control group (Non-PM group) or PM exposure group (PM group). After 6 weeks of PM exposure, the tendon DNA was extracted and anlyzed. Genome-wide DNA methylation profiles were determinen. DNA amplicons were prepared using Differential Methylation Hybridization (DMH) method, subsequently hybridized on to the Customized Agilent Rat CpG island Microarray. The goal was to unravel the DNA methylation patterns in different subgropus of tendon tissue according to partciulate matter exposure.

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tendon mRNA seq after particulate matter inhalation

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Oxidative Stress and Reduced Responsiveness of Challenged Circulating Leukocytes Following Pulmonary Instillation of Metal-Rich Particulate Matter in Rats

Project description:Exposure to welding fume consists of a mixed exposure of metal-rich particulate matter with gases (ozone, carbon monoxide) and/or vapors (VOCs). Data suggests that welders are immune compromised. Given the inability of pulmonary leukocytes to properly respond to a secondary infection, the question arose concerning how far upstream the dysfunction persisted. Our aim was to evaluate circulating leukocyte functionality after welding fume exposure. The results showed that welding fume exposure has rapid effects on the circulating leukocyte population as identified by relative mRNA expression changes. Instillation of MMA-SS reduced inflammatory protein production of circulating leukocytes when challenged with the secondary stimulus LPS. The effects were not related to transcription, but were observed in conjunction with oxidative stress. Rats were intratracheally instilled (ITI) with phosphate buffered saline or 2 mg of welding fume collected from a manual metal arc-stainles steel weld. Rats were sacrificed 4 and 24 h post-exposure and whole blood was collected. Whole blood was used for cellular differential counts, RNA isolation with subsequent microarray and Ingenuity Pathway Analysis, and secondary stimulation with lipopolysaccharide utilizing TruCulture technology from Myriad/Rules Based Medicine. Also, mononuclear cells were isolated 24 h post-exposure to measure oxidative stress by flow cytometry and confocal microscopy. Whole blood collected 4 and 24 h post-exposure was challenged (a paired non-stimulant (null) and stimulant (LPS) tube) for 24 h using Truculture technology from Myriad/ RBM. After the challenge, cells were recovered using RNA later for subsequent RNA isolation and microarray.

2014-06-15 | E-GEOD-58197 | biostudies-arrayexpress

Transcription profiling of mouse SP-C/TNF-Ia mice and their wildtype littermates to investigate the acute effects of particulate matter (EHC-93) inhalation in mice with chronic lung inflammation

Project description:We examined the impact of chronic lung inflammation on the pulmonary transcriptional response to inhaled urban particles. Transcript levels were measured using high density microarrays in total RNA isolated from whole lungs of wildtype and TNF-Î± overexpressing mice exposed by inhalation to particulate matter and euthanized immediately or 24 h post-exposure. Experiment Overall Design: Transgenic SP-C/TNF-Î± mice and their wildtype littermates were exposed by inhalation to particulate matter (0, 42 mg/m3 EHC-93) for 4 h and euthanized immediately or 24 h post-exposure (n=5 per treatment per time point, 40 animals total). Agilent 22K oligonucleotide microarrays were used to examine transcript levels in whole lung RNA. Stratagene Universal Mouse RNA was used as a reference.

2009-03-28 | E-GEOD-11037 | biostudies-arrayexpress

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