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Pleiotropic effects of negative energy balance in the postpartum dairy cow on splenic gene expression: repercussions for innate and adaptive immunity.

Morris DG, Waters SM, McCarthy SD, Patton J, Earley B, Fitzpatrick R, Murphy JJ, Diskin MG, Kenny DA, Brass A, Wathes DC - Physiol. Genomics (2009)

Bottom Line: Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology.SNEB increased systemic concentrations of NEFA and BHB, and white blood cell and lymphocyte numbers were decreased in SNEB animals.Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with NRF2-mediated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, natural killer cell signaling, p53 signaling, downregulation of IL-15, BCL-2, and IFN-gamma; upregulation of BAX and CHOP and increased apoptosis with a potential negative impact on innate and adaptive immunity.

View Article: PubMed Central - PubMed

Affiliation: Teagasc, Mellows Campus, Athenry, County Galway, Ireland. dermot.morris@teagasc.ie

ABSTRACT
Increased energy demands to support lactation, coupled with lowered feed intake capacity results in negative energy balance (NEB) and is typically characterized by extensive mobilization of body energy reserves in the early postpartum dairy cow. The catabolism of stored lipid leads to an increase in the systemic concentrations of nonesterified fatty acids (NEFA) and beta-hydroxy butyrate (BHB). Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology. The immune system is depressed in the peripartum period and early lactation and dairy cows are therefore more vulnerable to bacterial infections causing mastitis and or endometritis at this time. A bovine Affymetrix oligonucleotide array was used to determine global gene expression in the spleen of dairy cows in the early postpartum period. Spleen tissue was removed post mortem from five severe NEB (SNEB) and five medium NEB (MNEB) cows 15 days postpartum. SNEB increased systemic concentrations of NEFA and BHB, and white blood cell and lymphocyte numbers were decreased in SNEB animals. A total of 545 genes were altered by SNEB. Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with NRF2-mediated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, natural killer cell signaling, p53 signaling, downregulation of IL-15, BCL-2, and IFN-gamma; upregulation of BAX and CHOP and increased apoptosis with a potential negative impact on innate and adaptive immunity.

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Gene Network 3. Ingenuity pathway analysis shows a network of 27 focus genes with a significant score of 41. The network is displayed graphically as nodes (gene/gene products) and edges (the biological relationship between nodes). The node color intensity indicates the expression of genes: red upregulated, green downregulated in SNEB vs. MNEB spleen. The fold value is indicated under each node. The shapes of nodes indicate the functional class of the gene product, and the lines indicate the type of interaction (Supplementary Fig. S2).
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f4: Gene Network 3. Ingenuity pathway analysis shows a network of 27 focus genes with a significant score of 41. The network is displayed graphically as nodes (gene/gene products) and edges (the biological relationship between nodes). The node color intensity indicates the expression of genes: red upregulated, green downregulated in SNEB vs. MNEB spleen. The fold value is indicated under each node. The shapes of nodes indicate the functional class of the gene product, and the lines indicate the type of interaction (Supplementary Fig. S2).

Mentions: The third network (#3) with a score of 41 and 27 focus genes indicated gene clusters centered around interferon-γ (INFG), with main functions in immune response cell death and immunological disease (Fig. 4, Supplementary Table S5).


Pleiotropic effects of negative energy balance in the postpartum dairy cow on splenic gene expression: repercussions for innate and adaptive immunity.

Morris DG, Waters SM, McCarthy SD, Patton J, Earley B, Fitzpatrick R, Murphy JJ, Diskin MG, Kenny DA, Brass A, Wathes DC - Physiol. Genomics (2009)

Gene Network 3. Ingenuity pathway analysis shows a network of 27 focus genes with a significant score of 41. The network is displayed graphically as nodes (gene/gene products) and edges (the biological relationship between nodes). The node color intensity indicates the expression of genes: red upregulated, green downregulated in SNEB vs. MNEB spleen. The fold value is indicated under each node. The shapes of nodes indicate the functional class of the gene product, and the lines indicate the type of interaction (Supplementary Fig. S2).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2747343&req=5

f4: Gene Network 3. Ingenuity pathway analysis shows a network of 27 focus genes with a significant score of 41. The network is displayed graphically as nodes (gene/gene products) and edges (the biological relationship between nodes). The node color intensity indicates the expression of genes: red upregulated, green downregulated in SNEB vs. MNEB spleen. The fold value is indicated under each node. The shapes of nodes indicate the functional class of the gene product, and the lines indicate the type of interaction (Supplementary Fig. S2).
Mentions: The third network (#3) with a score of 41 and 27 focus genes indicated gene clusters centered around interferon-γ (INFG), with main functions in immune response cell death and immunological disease (Fig. 4, Supplementary Table S5).

Bottom Line: Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology.SNEB increased systemic concentrations of NEFA and BHB, and white blood cell and lymphocyte numbers were decreased in SNEB animals.Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with NRF2-mediated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, natural killer cell signaling, p53 signaling, downregulation of IL-15, BCL-2, and IFN-gamma; upregulation of BAX and CHOP and increased apoptosis with a potential negative impact on innate and adaptive immunity.

View Article: PubMed Central - PubMed

Affiliation: Teagasc, Mellows Campus, Athenry, County Galway, Ireland. dermot.morris@teagasc.ie

ABSTRACT
Increased energy demands to support lactation, coupled with lowered feed intake capacity results in negative energy balance (NEB) and is typically characterized by extensive mobilization of body energy reserves in the early postpartum dairy cow. The catabolism of stored lipid leads to an increase in the systemic concentrations of nonesterified fatty acids (NEFA) and beta-hydroxy butyrate (BHB). Oxidation of NEFA in the liver result in the increased production of reactive oxygen species and the onset of oxidative stress and can lead to disruption of normal metabolism and physiology. The immune system is depressed in the peripartum period and early lactation and dairy cows are therefore more vulnerable to bacterial infections causing mastitis and or endometritis at this time. A bovine Affymetrix oligonucleotide array was used to determine global gene expression in the spleen of dairy cows in the early postpartum period. Spleen tissue was removed post mortem from five severe NEB (SNEB) and five medium NEB (MNEB) cows 15 days postpartum. SNEB increased systemic concentrations of NEFA and BHB, and white blood cell and lymphocyte numbers were decreased in SNEB animals. A total of 545 genes were altered by SNEB. Network analysis using Ingenuity Pathway Analysis revealed that SNEB was associated with NRF2-mediated oxidative stress, mitochondrial dysfunction, endoplasmic reticulum stress, natural killer cell signaling, p53 signaling, downregulation of IL-15, BCL-2, and IFN-gamma; upregulation of BAX and CHOP and increased apoptosis with a potential negative impact on innate and adaptive immunity.

Show MeSH
Related in: MedlinePlus