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Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory mediators [391 expt: A549 vs BEAS 2B]

ABSTRACT: The goal of the study was to characterize gene expression profiles of lung epithelial and THP-1 monocytic cells influenzed by exposure to poultry dust extract. Gene expression profiles were determined by DNA microarrayanalysis using Illumina Human HT-12 v4 Expression bead chip, and changes in significantly induced transcripts validated by real time quantitative RT-PCR, ELISA, Western blotting and immunohistochemical staining. Significantly induced genes included IL-8, IL-6, ICAM-1, CCL2, CCL5, TLR4 and PTGS2. Pathway analysis indicated that dust extract treatment induced changes in gene expression influenced functions related to immune and inflammatory responses.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73061 | GEO | 2015/09/16

SECONDARY ACCESSION(S): PRJNA296128

REPOSITORIES: GEO

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Project description:The beneficial effects of mesenchymal stem cell administration have been reported in numerous preclinical studies. Briefly, decreased levels of Th2-related cytokines, namely IL-4, IL-5, and IL-13, impaired eosinophils infiltration, and mucus secretion within the lung have been recognized as hallmarks of MSC-mediated immunosuppression in OVA-Alumn- induced experimental model. However, to date, the effects of MSCs transfer on mixed airway inflammation remain elusive. Therefore, here we aimed to investigate the influence of internasal adipose tissue-derived MSCs on mixed inflammation in a house dust mite (HDM) extract-induced experimental asthma model. To induce mixed airway inflammation, mice were challenged with 10 g of HDM extract for 5 days each week. Additionally, to investigate the short- and long-term effects, adipose tissue-derived MSCs were administrated at two-time points. To analyze MSC-mediated changes, we assessed lung morphology, frequencies of T cells effectors, epithelial barrier integrity, lung transcriptomic profiles, and the levels of cytokines and chemokine in bronchoalveolar lavage (BAL). We observed the limitation of cellular infiltration and mucus production after MSCs administration. Moreover, we noted a trend to decrease in the frequencies of T cells producing IL-4 and IFNy as a long-term effect of MSCs administration. Additionally, the expression of ZO-1 was increased in both analyzed time-points of MSCs transfer. Notably, we found the changes in the transcriptomic profiles reflecting, the inflammation of the respiratory system, the proliferation of lymphocytes, migration of leukocytes, and recruitment of neutrophils and eosinophils. Finally, we also noted the differences in the levels of CXCL and CCL chemokines in BAL between short- and long-term models, while the changes in Th2-related cytokines levels were limited. Overall, here we confirmed the therapeutic potential of adipose tissue-derived MSCs administration in a novel HDM extract-induced experimental model of mixed airway inflammation.

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Gene expression profiling of the effects of organic dust in lung epithelial and THP-1 cells reveals inductive effects on inflammatory mediators [391 expt: A549 vs BEAS 2B]

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