Identification of potential biomarkers from gene expression profiles in rat lungs intratracheally instilled with C60 fullerenes

Fujita, Katsuhide; Morimoto, Yasuo; Endoh, Shigehisa; Uchida, Kunio; Fukui, Hitoshi; Ogami, Akira; Tanaka, Isamu; Horie, Masanori; Yoshida, Yasukazu; Iwahashi, Hitoshi; Nakanishi, Junko

doi:10.1016/j.tox.2010.05.004

Cited by 23 publications

(19 citation statements)

References 15 publications

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“…Gene expression analysis is expected to elucidate the toxicological effects of nanomaterials relevant to specific histopathological phenotypes. We have previously analyzed gene expression profiles in rat lungs after intratracheal instillation of C 60 fullerenes (Fujita et al., 2009a , 2010 ). The gene expression profiles demonstrated marked correspondence with results from other conventional methods such as immunohistochemical and BALF cell analysis.…”

Section: Introductionmentioning

confidence: 99%

Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression

et al. 2014

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The use of carbon nanotubes in the industry has grown; however, little is known about their toxicological mechanism of action. Single-wall carbon nanotube (SWCNT) suspensions were administered by single intratracheal instillation in rats. Persistence of alveolar macrophage-containing granuloma was observed around the sites of SWCNT aggregation at 90 days post-instillation in 0.2-mg- or 0.4-mg-injected doses per rat. Meanwhile, gene expression profiling revealed that a large number of genes involved in the inflammatory response were markedly upregulated until 90 days or 180 days post-instillation. Subsequently, gene expression patterns were dramatically altered at 365 days post-instillation, and the number of upregulated genes involved in the inflammatory response was reduced. These results suggested that alveolar macrophage-containing granuloma reflected a characteristic of the histopathological transition period from the acute-phase to the subchronic-phase of inflammation, as well as pulmonary acute phase response persistence up to 90 or 180 days after intratracheal instillation in this experimental setting. The expression levels of the genes Ctsk, Gcgr, Gpnmb, Lilrb4, Marco, Mreg, Mt3, Padi1, Slc26a4, Spp1, Tnfsf4 and Trem2 were persistently upregulated in a dose-dependent manner until 365 days post-instillation. In addition, the expression levels of Atp6v0d2, Lpo, Mmp7, Mmp12 and Rnase9 were significantly upregulated until 754 days post-instillation. We propose that these persistently upregulated genes in the chronic-phase response following the acute-phase response act as potential biomarkers in lung tissue after SWCNT instillation. This study provides further insight into the time-dependent changes in genomic expression associated with the pulmonary toxicity of SWCNTs.

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Section: Introductionmentioning

confidence: 99%

Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression

et al. 2014

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“…Pendrin up-regulation is seen in: 1) airway epithelial cultures chronically exposed to cytokines, including IL-4, IL-13, and IL-17A; 2) rodent models of inflammatory lung disease, including allergen (ovalbumin)-induced asthma, chronic obstructive pulmonary disease, infection, and industrial toxin exposure; and 3) humans with rhinovirus infection, asthma, cystic fibrosis (CF), rhinitis, and chronic rhinosinusitis (10,11,(17)(18)(19)(20)(21)(22)(23)(24)(25). Pendrin knockout is also associated with reduced lung inflammation in a murine model of Bordetella pertussis lung infection (26).…”

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Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis

Haggie

Phuan²,

Tan³

et al. 2016

FASEB j.

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Pendrin (SLC26A4) is a Cl 2 /anion exchanger expressed in the epithelium of inflamed airways where it is thought to facilitate Cl 2 absorption and HCO 3 2 secretion. Studies using pendrin knockout mice and airway epithelial cells from hearing-impaired subjects with pendrin loss of function suggest involvement of pendrin in inflammatory lung diseases, including cystic fibrosis (CF), perhaps by regulation of airway surface liquid (ASL) volume. Here we identified small-molecule pendrin inhibitors and demonstrated their efficacy in increasing ASL volume. A cell-based, functional high-throughput screen of ∼36,000 synthetic small molecules produced 3 chemical classes of inhibitors of human pendrin. After structure-activity studies, tetrahydropyrazolopyridine and pyrazolothiophenesulfonamide compounds reversibly inhibited pendrin-facilitated Cl 2 exchange with SCN 2 , I 2 , NO 3 2 , and HCO 3 2 with drug concentration causing 50% inhibition down to ∼2.5 mM. In well-differentiated primary cultures of human airway epithelial cells from non-CF and CF subjects, treatment with IL-13, which causes inflammation with strong pendrin up-regulation, strongly increased Cl 2 /HCO 3 2 exchange and the increase was blocked by pendrin inhibition. Pendrin inhibition significantly increased ASL depth (by ∼8 mm) in IL-13-treated non-CF and CF cells but not in untreated cells. These studies implicate the involvement of pendrin-facilitated Cl 2 / HCO 3 2 in the regulation of ASL volume and suggest the utility of pendrin inhibitors in inflammatory lung diseases, including CF

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“…Intermediary organic solvents are often used and subsequently removed by evaporation; 6 (c) encapsulation of C 60 with carriers, such as g-cyclodextrine (g-CD) 7 and surfactants. 8 The latter two methods are relatively effective. However, the residual toxic organic solventsor the coexistent carriers in the C 60 aqueous solution often result in negative effects on the biological activities of C 60 .…”

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Solubilization of pristine fullerene by the unfolding mechanism of bovine serum albumin for cytotoxic application

Lin

Wang

et al. 2011

Chem. Commun.

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Identification of potential biomarkers from gene expression profiles in rat lungs intratracheally instilled with C60 fullerenes

Cited by 23 publications

References 15 publications

Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression

Intratracheal instillation of single-wall carbon nanotubes in the rat lung induces time-dependent changes in gene expression

Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis

Solubilization of pristine fullerene by the unfolding mechanism of bovine serum albumin for cytotoxic application

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