Staphylococcus aureus and Lipopolysaccharide Modulate Gene Expressions of Drug Transporters in Mouse Mammary Epithelial Cells Correlation to Inflammatory Biomarkers

Yagdiran, Yagmur; Tallkvist, Jonas; Artursson, Karin; Oskarsson, Agneta

doi:10.1371/journal.pone.0161346

Cited by 12 publications

(6 citation statements)

References 67 publications

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“…Pro-inflammatory cytokines, chemokines such as CXCL2, CCL20, and GRO1(CXCL1) have important roles in immune responses due to modulation of leukocyte infiltration (neutrophils and monocytes). CXCL2 has been determined as a biomarker of the inflammatory reaction previously [ 87 ]. It has been suggested that CXCL1 can be used as therapeutic targets, therapeutics, or biomarkers in mastitis [ 88 ].…”

Section: Discussionmentioning

confidence: 99%

Integration of machine learning and meta-analysis identifies the transcriptomic bio-signature of mastitis disease in cattle

et al. 2018

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Gram-negative bacteria such as Escherichia coli (E. coli) are assumed to be among the main agents that cause severe mastitis disease with clinical signs in dairy cattle. Rapid detection of this disease is so important in order to prevent transmission to other cows and helps to reduce inappropriate use of antibiotics. With the rapid progress in high-throughput technologies, and accumulation of various kinds of ‘-omics’ data in public repositories, there is an opportunity to retrieve, integrate, and reanalyze these resources to improve the diagnosis and treatment of different diseases and to provide mechanistic insights into host resistance in an efficient way. Meta-analysis is a relatively inexpensive option with good potential to increase the statistical power and generalizability of single-study analysis. In the current meta-analysis research, six microarray-based studies that investigate the transcriptome profile of mammary gland tissue after induced mastitis by E. coli infection were used. This meta-analysis not only reinforced the findings in individual studies, but also several novel terms including responses to hypoxia, response to drug, anti-apoptosis and positive regulation of transcription from RNA polymerase II promoter enriched by up-regulated genes. Finally, in order to identify the small sets of genes that are sufficiently informative in E. coli mastitis, the differentially expressed gene introduced by meta-analysis were prioritized by using ten different attribute weighting algorithms. Twelve meta-genes were detected by the majority of attribute weighting algorithms (with weight above 0.7) as most informative genes including CXCL8 (IL8), NFKBIZ, HP, ZC3H12A, PDE4B, CASP4, CXCL2, CCL20, GRO1(CXCL1), CFB, S100A9, and S100A8. Interestingly, the results have been demonstrated that all of these genes are the key genes in the immune response, inflammation or mastitis. The Decision tree models efficiently discovered the best combination of the meta-genes as bio-signature and confirmed that some of the top-ranked genes -ZC3H12A, CXCL2, GRO, CFB- as biomarkers for E. coli mastitis (with the accuracy 83% in average). This research properly indicated that by combination of two novel data mining tools, meta-analysis and machine learning, increased power to detect most informative genes that can help to improve the diagnosis and treatment strategies for E. coli associated with mastitis in cattle.

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Section: Discussionmentioning

confidence: 99%

Integration of machine learning and meta-analysis identifies the transcriptomic bio-signature of mastitis disease in cattle

et al. 2018

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“…In a rat model of rheumatoid arthritis, there was an 85% increase in the duodenal permeability of a Chinese herbal medication, which was apparently due to a downregulation of membrane P-gp activity (Duan et al, 2017). In contrast, P-gp upregulation was observed during the assessment of an in vitro murine model of bovine mastitis caused by E. coli (reflected in the administration of LPS) or Staphylococcus aureus (Yagdiran et al, 2016). Murine mammary epithelial HC11 cells differentiated into a secreting phenotype exhibited a statistically significant increase in P-gp expression when incubated with LPS and S. aureus as compared with that associated with the control cell cultures.…”

Section: Studying Mechanisms Underlying Disease-induced Pk Changesmentioning

confidence: 98%

“…Murine mammary epithelial HC11 cells differentiated into a secreting phenotype exhibited a statistically significant increase in P-gp expression when incubated with LPS and S. aureus as compared with that associated with the control cell cultures. This outcome was interpreted as reflecting potential increases in drug and toxin secretion into the milk of lactating dairy cattle (Yagdiran et al, 2016).…”

Section: Studying Mechanisms Underlying Disease-induced Pk Changesmentioning

confidence: 99%

The Impact of Infection and Inflammation on Drug Metabolism, Active Transport, and Systemic Drug Concentrations in Veterinary Species

et al. 2020

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Within human medicine, it is recognized that the pharmacokinetics (PK) of many compounds can be altered by the presence of inflammation or infection. Research into the reason for these changes has identified pathways that can influence drug absorption, clearance, and tissue distribution. In contrast, far less is known about these relationships within the framework of veterinary medicine. Rather, most of the PK data generated in veterinary species employs healthy subjects, raising the question of whether these studies are founded on an assumption that healthy animal PK reflect that of the diseased animal population. Accordingly, there is a need to explore the PK changes that might be overlooked in studies that recruit only healthy animals to assesses drug PK. To meet this objective, we surveyed the published literature for studies focusing on the impact of disease on the dose-exposure relationships in food-producing and companion animal species. We found that, consistent with humans and laboratory species, both up-and downregulation of the various cytochrome isoenzymes and/or transporters have occurred in response to an increase in inflammatory mediators. These findings suggest that, as observed in human medicine, the potential for differences in the drug PK in healthy versus animal patients points to a need for acquiring a greater understanding of these changes and how they may influence the dose-exposureresponse relationships of veterinary pharmaceuticals. SIGNIFICANCE STATEMENTThis review delivers a much-needed summary of published information that provides insights into how disease and inflammation can influence the appropriateness of extrapolating laboratorybased dose-exposure-response relationships to what will occur in the actual veterinary patient. As part of this review, we also examine some of the method-associated issues to be considered when assessing the reported nature and magnitude of these changes.

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“…Moreover, Cp activates pathogen recognition in dairy cows that intramammary challenged with E. coli lipopolysaccharide [34]. Similarly, when treating mammary epithelial cells of murine with E. coli endotoxin or lipopolysaccharide S. aureus, up-regulation and transportation of some inflammatory marker genes are affected [35]. Both milk Cp and SAA levels depend on the method of measurement to be diagnostic tools for subclinical mastitis and many inflammatory diseases in dairy cattle [7,36].…”

Section: Escherichia Coli Staphylococcus Aureusmentioning

confidence: 99%

Serum Amyloid A4 and Ceruloplasmin Evaluated Mastitic Cattle with Escherichia coli or Staphylococcus aureus including Resistant Genes

Farag¹,

Abd-El-Moaty²,

Ibrahim³

et al. 2017

J Bioanal Biomed

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Staphylococcus aureus and Lipopolysaccharide Modulate Gene Expressions of Drug Transporters in Mouse Mammary Epithelial Cells Correlation to Inflammatory Biomarkers

Cited by 12 publications

References 67 publications

Integration of machine learning and meta-analysis identifies the transcriptomic bio-signature of mastitis disease in cattle

Integration of machine learning and meta-analysis identifies the transcriptomic bio-signature of mastitis disease in cattle

The Impact of Infection and Inflammation on Drug Metabolism, Active Transport, and Systemic Drug Concentrations in Veterinary Species

Serum Amyloid A4 and Ceruloplasmin Evaluated Mastitic Cattle with Escherichia coli or Staphylococcus aureus including Resistant Genes

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