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Cellular and molecular effects of iron-based pigments on macrophages

ABSTRACT: Tattoos are becoming increasingly popular across generations, with 10-20% of the population in Europe and the United States bearing at least one tattoo. Tattoos represent an intradermal injection of pigments (i.e. coloured insoluble micro- and nano-particles), which remain in place throughout life. Although tattoos have existed for centuries, the question of their health impact has really arisen rather lately, so that a significant gap in our understanding of the cellular and molecular long-term effects of these pigments on the body remains. In this project, we investigate a wide range of tattoo pigments on macrophages. Macrophages, pivotal in pigment persistence through phagocytic processes and capture-release-recapture cycles, are also key players in the inflammatory response and tissue homeostasis. Dysregulation in macrophage functionalities can potentially lead to substantial health consequences such as deficient immune response or such as sarcoidosis. To assess the long-term effects of tattoos, we tested iron-based pigments (which are widely used in the medical field for dermopigmentation of the nipple-areola complex after mastectomy) using an exposure scheme consisting in an acute exposure for 24 hours and a 5-days post exposure recovery period. Proteomic analyses were conducted to understand the underlying cellular mechanisms.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Macrophage

SUBMITTER: Hélène Diemer

LAB HEAD: Christine Carapito

PROVIDER: PXD064985 | Pride | 2025-10-09

REPOSITORIES: Pride

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Project description:Sulfur mustard (SM) is a potent alkylating agent. We are developing medical countermeasures to reduce the injury caused by SM exposure. Screening in the mouse ear vesicant model has identified three effective compounds: dimercaprol (British anti-lewisite), indomethacin, and octyl homovanillamide (OHV). To identify gene expression changes that correlate with compound efficacy we used oligonucleotide microarrays to compare gene expression profiles in vehicle-exposed skin, SM-exposed skin, and skin pretreated with each compound before SM exposure. Mice were topically exposed on the inner surface of the right ear to SM alone or pretreated for 15 min with one of the compounds and then exposed to SM. Left ears were vehicle-exposed. Ear tissue was harvested 24 hr later for ear weight determination (an endpoint indicating compound efficacy). The exposure groups were: methylene chloride (sulfur mustard vehicle); ethanol (drug vehicle); 0.08 mg sulfur mustard; 6.25 mg dimercaprol 15 min before 0.08 mg sulfur mustard; 1.34 mg indomethacin 15 min before 0.08 mg sulfur mustard; 0.6 mg octylhomovanillamide 15 min before 0.08 mg sulfur mustard; 6.25 mg dimercaprol alone; 1.34 mg indomethacin alone; 0.6 mg octylhomovanillamide alone. RNA was extracted from the tissues and used to generate oligonucleotide microarray probes. Principal component analysis of the gene expression data revealed partitioning of the samples based on drug treatment and SM exposure. Vehicle-exposed mouse ears clustered away from the other treatment groups. SM-exposed mouse ears pretreated with dimercaprol or OHV clustered more closely with vehicle-exposed ears, while SM-exposed mouse ears pretreated with indomethacin clustered more closely with SM-exposed ears. This clustering of the samples is supported by the ear weight data, in which the indomethacin group has ear weights closer to the SM-exposed group, whereas the dimercaprol and OHV groups have ear weights closer to the vehicle-exposed group. Correlation coefficients were calculated for each gene based on the correlation between gene expression level and ear weight. These data provide the basis for understanding what gene expression changes are important in the development of effective SM medical countermeasures. Experiment Overall Design: Exposure of mouse ears to sulfur mustard alone, sulfur mustard preceded by drug treatment, or vehicle compounds. Naive controls were also included. Biological replicates of at least n=3 were examined for each exposure condition.

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	QE45459HD.mgf	Mgf
	QE45459HD.raw	Raw
	QE45461HD.mgf	Mgf
	QE45461HD.raw	Raw
	QE45463HD.mgf	Mgf

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Cellular and molecular effects of iron-based pigments on macrophages

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