Impact of intramammary treatment on gene expression profiles in bovine Escherichia coli mastitis.
Clinical mastitis caused by E. coli accounts for significant production losses and animal welfare concerns on dairy farms worldwide. The benefits of therapeutic intervention in mild to moderate cases are incompletely understood. We investigated the effect of intramammary treatment with cefapirin alone or in combination with prednisolone on gene expression profiles in experimentally-induced E. coli mastitis in six mid-lactating Holstein Friesian cows. Cows were challenged with E. coli in 3 quarters and received 4 doses of 300 mg cefapirin in one quarter and 4 doses of 300 mg cefapirin together with 20 mg prednisolone in another quarter. At 24 h (n = 3) or 48 h (n = 3) post-challenge, tissue samples from control and treated quarters were collected for microarray analysis. Gene expression analysis of challenged, un-treated quarters revealed an up-regulation of transcripts associated with immune response functions compared to un-challenged quarters. Both treatments resulted in down-regulation of these transcripts compared to challenged, un-treated quarters most prominently for genes representing Chemokine and TLR-signaling pathways. Gene expression of Lipopolysaccharide Binding Protein (LBP), CCL2 and CXCL2 were only significantly down-regulated in cefapirin-prednisolone-treated quarters compared to un-treated controls. Down-regulation of chemokines was further confirmed on the basis of protein levels in milk whey for CXCL1, CXCL2 and CXCL8 in both treatments with a greater decrease in cefapirin-prednisolone-treated quarters. The data reveal a significant effect of treatment on cell recruitment with a more pronounced effect in cefapirin-prednisolone treated quarters. Provided a rapid bacteriological clearance, combination therapy may prevent neutrophil-induced tissue damage and promote recovery of the gland.
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Anja
A
Sipka
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Suzanne
S
Klaessig
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Gerald E
GE
Duhamel
GD Animal Health Center, Deventer, The Netherlands.
Jantijn
J
Swinkels
INRA, UMR1282, Infectiologie Animale et Santé Publique, Nouzilly, France ; Université François Rabelais de Tours, UMR1282 ISP, Tours, France.
Pascal
P
Rainard
Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, United States of America.
Ynte
Y
Schukken
D000818:Animals; D002417:Cattle; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002514:Cephapirin / Q000494:pharmacology / Q000627:therapeutic use; D016207:Cytokines / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects / Q000502:physiology*; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000235:genetics / Q000276:immunology / Q000662:veterinary*; D005260:Female; D020869:Gene Expression Profiling; D008321:Mammary Glands, Animal / Q000187:drug effects* / Q000382:microbiology*; D008414:Mastitis, Bovine / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D008892:Milk / Q000187:drug effects / Q000378:metabolism; D011239:Prednisolone / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D013997:Time Factors; D059467:Transcriptome / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D002514:Cephapirin; D011239:Prednisolone