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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).

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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.

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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

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