Publikationsdatenbank

Ex vivo models for the exploration of innovative treatments for bovine mastitis (2023)

Art

Vortrag

Autoren

Filor, V. (WE 14)

Brand, K. S. (WE 14)

Kühn, C.

Bäumer, W. (WE 14)

Kongress

15th International Congress of the European Association for Veterinary Pharmacology and Toxicology

Bruges, Belgium, 02. – 05.07.2023

Quelle

Journal of veterinary pharmacology and therapeutics

Bandzählung: 46

Heftzählung: S1

Seiten: 76 – 77

ISSN: 1365-2885

Sprache

Englisch

Verweise

URL (Volltext): https://onlinelibrary.wiley.com/doi/10.1111/jvp.13264

DOI: 10.1111/jvp.13264

Kontakt

Institut für Pharmakologie und Toxikologie

Koserstr. 20
14195 Berlin
+49 30 838 53221
pharmakologie@vetmed.fu-berlin.de

Abstract / Zusammenfassung

Introduction:
Mastitis in cattle is a worldwide problem with economic impact as well as consequences for animal welfare. Furthermore, the often-low cure rates in cattle and potential antibiotic residues in milk may exacerbate the problem of antimicrobial resistance. Therefore, we have established ex vivo models to examine pathophysiological processes in order to investigate a broad spectrum of potential pharmacological interventions against mastitis.

Patients and Methods:
Mammary glands from Holstein Friesian cows were collected immediately after slaughtering. For the isolated perfused udder Tyrode's solution was used as nutrient solution. The rear quarter was intracisternally challenged with 108 CFU/mL of S. uberis. The fore quarter was used as an untreated control. Tissue samples from the gland cistern and udder base were collected after 6 h. Real-time PCR with following gene expression analysis was implemented for TNF-α, CCL20, CXCL8, IL-10, LAP, S100A9, IL-1β, IL-6 and GAPDH as housekeeping gene. On the protein level we analyzed the samples with IL-6 and IL-1ß ELISA. We also performed transcriptome analysis to evaluate transcriptional changes. Tissue viability was checked every 2 h.

Results:
In the perfused isolated udder, a general increase of pro-inflammatory mediators was detected 6 h after S. uberis instillation and became significant for different genes in real-time PCR analyses. In the gland cistern CCL20 was significantly upregulated as wells as CXCL8 in the udder base. At protein level a significant increase in the infected udder quarter was only seen for IL-1ß in the udder base, but no increase for IL-6. Interestingly, the transcriptome analysis also showed, that the most up-regulated genes are typically those expressed in early mammalian development, like KLF2 and KLF4. Almost no increase of pro-inflammatory genes was seen.

Conclusions:
We compared these results with the results of our previous studies where we treated the udder with LPS and observed a significant increase in most genes after 6 h. For studies on mastitis after inoculation of gram-positive bacteria, a larger time frame for sampling would probably need to be chosen. Precision cut bovine udder slices could then be used for this purpose. In future studies we also want to have a closer look to other possible pathways which were revealed by the transcriptome analysis, Although the results of the mastitis studies vary in the different models, they are remarkably complementary and can be used for studies aimed at better understanding the pathophysiological processes in mastitis, as well as for investigating alternative therapies.