TY - JOUR

T1 - Short communication

T2 - Staphylococcus aureus infection modulates expression of drug transporters and inflammatory biomarkers in mouse mammary gland

AU - Oskarsson, A.

AU - Yagdiran, Y.

AU - Nazemi, S.

AU - Tallkvist, J.

AU - Knight, C. H.

PY - 2017/3

Y1 - 2017/3

N2 - Mastitis is the most common disease in dairy herds worldwide and is often caused by Staphylococcus aureus. Little is known about the effect of mastitis on transporters in the mammary gland and the effect on transporter-mediated secretion of drugs into milk. We studied gene expressions of ATP-binding cassette and solute carrier transporters in S. aureus-infected mammary glands of mice. On d 7 of lactation, NMRI mice were inoculated with 1,000 cfu of S. aureus in 2 mammary glands and with a saline vehicle in 2 control glands. Gene expression of the transporters, Bcrp, Mdr1, Mrp1, Oatp1a5, Octn1, and Oct1, and of Csn2, the gene encoding β-casein, were determined in mammary glands at 72 h after treatment. As biomarkers of the inflammatory response gene, expressions of the cytokines Il6, Tnfα, and the chemokine Cxcl2 were measured. Despite a high individual variation between the 6 animals, some characteristic patterns were evident. The 3 inflammatory biomarkers were upregulated in all animals; Csn2 was downregulated compared with controls in all animals, although not statistically significantly. Both Mrp1 and Oatp1a5 were statistically significantly upregulated and Bcrp was downregulated. Gene expression of Bcrp followed the expression of Csn2 in each of the animals, indicating a possible co-regulation. The findings demonstrate that S. aureus infection has an effect on expression of drug transporters in the mammary gland, which may affect secretion of drugs into milk and efficacy of drug therapy.

AB - Mastitis is the most common disease in dairy herds worldwide and is often caused by Staphylococcus aureus. Little is known about the effect of mastitis on transporters in the mammary gland and the effect on transporter-mediated secretion of drugs into milk. We studied gene expressions of ATP-binding cassette and solute carrier transporters in S. aureus-infected mammary glands of mice. On d 7 of lactation, NMRI mice were inoculated with 1,000 cfu of S. aureus in 2 mammary glands and with a saline vehicle in 2 control glands. Gene expression of the transporters, Bcrp, Mdr1, Mrp1, Oatp1a5, Octn1, and Oct1, and of Csn2, the gene encoding β-casein, were determined in mammary glands at 72 h after treatment. As biomarkers of the inflammatory response gene, expressions of the cytokines Il6, Tnfα, and the chemokine Cxcl2 were measured. Despite a high individual variation between the 6 animals, some characteristic patterns were evident. The 3 inflammatory biomarkers were upregulated in all animals; Csn2 was downregulated compared with controls in all animals, although not statistically significantly. Both Mrp1 and Oatp1a5 were statistically significantly upregulated and Bcrp was downregulated. Gene expression of Bcrp followed the expression of Csn2 in each of the animals, indicating a possible co-regulation. The findings demonstrate that S. aureus infection has an effect on expression of drug transporters in the mammary gland, which may affect secretion of drugs into milk and efficacy of drug therapy.

KW - mastitis

KW - drug transporters

KW - mammary gland

KW - Staphylococcus aureus

U2 - 10.3168/jds.2016-11650

DO - 10.3168/jds.2016-11650

M3 - Letter

C2 - 28088425

VL - 100

SP - 2375

EP - 2380

JO - Journal of Dairy Science

JF - Journal of Dairy Science

SN - 0022-0302

IS - 3

ER -