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

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. © 2012 erdely et al.; licensee biomed central ltd.