Differential calcium signaling in dairy cows with specific CXCR1 genotypes potentially related to interleukin-8 receptor functionality |
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Authors: | M Rambeaud G M Pighetti |
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Institution: | (1) Department of Animal Science, The University of Tennessee, 114 McCord Hall, 2640 Morgan Circle, Knoxville, TN 37996, USA |
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Abstract: | Neutrophil migration and activation are critical components of innate immunity and are mediated by a variety of inflammatory
mediators, which include interleukin-8 (IL-8) and epithelial-derived neutrophil activating peptide-78 (ENA-78). Limited knowledge
on the expression of receptors for these inflammatory mediators (CXCR1 and CXCR2) in bovine, in addition to the association
of a polymorphism (G→C) in position +777 of the CXCR1 gene with impaired neutrophil function, prompted evaluation of CXCR1 and CXCR2 mRNA and protein expression, ligand binding
affinity, and intracellular receptor signaling in neutrophils from cows with different CXCR1 genotypes. Initial observations
revealed that overall IL-8 receptor numbers appeared to be lower in cows with a CC genotype compared to cows with a GG genotype.
However, in the presence of SB225002, a CXCR2 inhibitor, CXCR1 affinity was about fivefold lower in cows with a CC genotype
and may have resulted in an underestimation of receptor numbers in cows with this genotype.
In addition, intracellular calcium (Ca++]i) release was lower in cows with a CC genotype when cells were stimulated with IL-8 but not ENA-78. Furthermore, when neutrophils
were stimulated with an optimal dose of IL-8 in the presence of SB225002, Ca++]i release was lower in cows with a CC genotype, suggesting differential CXCR1 signaling among genotypes. These findings offer
knowledge of the role that each of these receptors plays in the inflammatory response in the bovine and provide insight into
the potential mechanisms that may be affected in neutrophils of cows with different CXCR1 genotypes. |
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Keywords: | Neutrophil Bovine CXCR1 Interleukin-8 Intracellular Ca++ |
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