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- Title
Type I interferon and pattern recognition receptor signaling following particulate matter inhalation.
- Authors
Erdely, Aaron; Antonini, James M.; Salmen-Muniz, Rebecca; Liston, Angie; Hulderman, Tracy; Simeonova, Petia P.; Kashon, Michael L.; Shengqiao Li; Ja K. Gu; Stone, Samuel; Chen, Bean T.; Frazer, David G.; Zeidler-Erdely, Patti C.
- Abstract
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 α and β 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.
- Subjects
PARTICULATE matter; INTERFERONS; PATTERN perception; INFLAMMATION; BLOOD cells
- Publication
Particle & Fibre Toxicology, 2012, Vol 9, Issue 1, p25
- ISSN
1743-8977
- Publication type
Article
- DOI
10.1186/1743-8977-9-25