Unknown,Transcriptomics,Genomics,Proteomics

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Inhalation of rod-like carbon nanotubes causes unconventional asthma

ABSTRACT: Exposure to rod-shaped carbon nanotubes reveals novel innate immunity mediated asthma-like inflammation in mice. Inhalation of rCNT elicited a drastic infiltration of eosinophils into the lungs but only minor infiltration of neutrophils and lymphocytes. Transcriptomic study revealed remarkable effects of rCNT exposure, affecting almost exclusively pathways essential for innate immunity. Mice were exposed to rCNT or tCNT for 4 h and sacrificed immediately or 24 h after the exposure. The total RNA was extracted from lung samples, hybridized to Agilent microarray and analyzed with BioConductor package Limma. Untreated mice were used as control.

ORGANISM(S): Mus musculus

SUBMITTER: Dario Greco

PROVIDER: E-GEOD-50176 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Rationale: Previous work demonstrated that pre-exposure to ozone primes innate immunity and increases TLR4-mediated response to subsequent stimulation with lipopolysaccharide (LPS). To further explore the pulmonary innate immune response to ozone exposure, we investigated the effect of ozone in combination with Pam3CYS, a synthetic TLR2/TLR1 agonist. Methods: Bronchoalveolar lavage (BAL) and lungs were harvested from C57Bl/6 mice after exposure to ozone or filtered air followed by saline or Pam3CYS 24 hours later. Cells and cytokines in the BAL, surface expression of TLRs on macrophages, and lung RNA genomic expression profiles were examined. Results: We demonstrate an increased BAL cell influx, increased IL-6 and KC, and decreased MIP-1α and TNF-α in response to Pam3CYS as a result of ozone pre-exposure. We also observed increased cell surface expression of TLR4, TLR2 and TLR1 on macrophages as a result of ozone alone or in combination with Pam3CYS. Gene expression analysis of lung tissue revealed a significant increase in expression of genes related to injury repair and cell cycle as a result of ozone exposure. When comparing Pam3CYS treated animals to saline treated animals with or without ozone, genes associated with inflammation were significantly increased. Potentially novel ozone exposure candidate genes (CCK, RELM-α and β) were identified. Conclusion: Our results extend previous findings with ozone/LPS to other TLRs PAMPs and suggest that ozone priming of innate immunity is a general mechanism. Gene expression profiling of lung tissue identified transcriptional networks and genes that contribute to the priming of innate immunity at the molecular level. Mice were exposed to either 2ppm ozone or filtered air (FA) for 3 hours. 24 hours following ozone exposure, mice from either the ozone or FA group were treated intratracheally with either 100ug of Pam3CYS in saline or saline alone. Animals were euthanized 4 or 24 hours post-Pam3CYS exposure. RNA from whole lung tissue from 4 animals per group was profiled.

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Inhalation of rod-like carbon nanotubes causes unconventional asthma

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