Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows

Pegbovigrastim is a commercial long-acting analog of bovine granulocyte colony-stimulating factor (rbG-CSF) that promotes the increased count and functionality of polymorphonuclear cells in dairy cows around the time of parturition. We hypothesized that pegbovigrastim administered to periparturient...

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Main Authors: Vincenzo Lopreiato, Ernesto Palma, Andrea Minuti, Juan J. Loor, Mariangela Lopreiato, Francesca Trimboli, Valeria Maria Morittu, Anna Antonella Spina, Domenico Britti, Erminio Trevisi
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Language:English
Published: MDPI AG 2020-04-01
Series:Animals
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Online Access:https://www.mdpi.com/2076-2615/10/4/621
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author Vincenzo Lopreiato
Ernesto Palma
Andrea Minuti
Juan J. Loor
Mariangela Lopreiato
Francesca Trimboli
Valeria Maria Morittu
Anna Antonella Spina
Domenico Britti
Erminio Trevisi
author_facet Vincenzo Lopreiato
Ernesto Palma
Andrea Minuti
Juan J. Loor
Mariangela Lopreiato
Francesca Trimboli
Valeria Maria Morittu
Anna Antonella Spina
Domenico Britti
Erminio Trevisi
author_sort Vincenzo Lopreiato
collection DOAJ
description Pegbovigrastim is a commercial long-acting analog of bovine granulocyte colony-stimulating factor (rbG-CSF) that promotes the increased count and functionality of polymorphonuclear cells in dairy cows around the time of parturition. We hypothesized that pegbovigrastim administered to periparturient cows at approximately seven days before parturition and within 24 hours after calving could affect the profiles of gene networks involved in leukocyte function. Blood was collected on Day 3 after calving from treated groups (pegbovigrastim (PEG); 13 Simmental (seven multiparous and six primiparous) and 13 Holstein (seven multiparous and six primiparous) cows) that received pegbovigrastim (Imrestor; Elanco Animal Health) and controls (CTR; 13 Simmental (seven multiparous and six primiparous) and 13 Holstein (six multiparous and seven primiparous) cows) that received saline solution. Blood from all cows was sampled from the jugular vein in a PAXgene Blood RNA System tube (Preanalytix, Hombrechtikon, Switzerland) for RNA extraction. The RT-qPCR analysis was performed to investigate a panel of 34 genes of interest, representing recognition, immune mediation, migration, cell adhesion, antimicrobial strategies, inflammatory cascade, oxidative pattern, and leukotrienes in whole blood leukocytes. Normalized data were subjected to the MIXED model of SAS (ver. 9.4) with treatment, breed, parity, and their interaction as fixed effects. Compared with CTR, whole blood leukocytes of PEG cows had higher expression of genes involved in recognition and immune modulation (<i>CD14</i>, <i>CD16</i>, <i>MYD88</i>, <i>TLR2</i>, and <i>TLR4</i>), cell adhesion (<i>ITGB2</i>, <i>ITGAL</i>, <i>TLN1</i>, <i>SELL</i>, <i>SELPLG</i>, and <i>CD44</i>), antimicrobial activity (<i>MMP9</i>, <i>LTF</i>, and <i>LCN2</i>), and inflammatory cascade (<i>CASP1</i>, <i>TNFRSF1A</i>, <i>IL1B</i>, <i>IL1R</i>, <i>IL18</i>, <i>IRAK1</i>, <i>NLRP3</i>, and <i>S100A8</i>). This suggested an improvement of migration, adhesion, and antimicrobial ability and an enhanced inflammatory response, which in turn could trigger immune cell activation and enhance function. Expression of <i>SOD2</i> and <i>ALOX5</i> was also greater in the PEG group. In contrast, compared with CTR cows, PEG led to lower expression of <i>RPL13A</i>, <i>ALOX15</i>, <i>IL8</i>, and <i>TNF</i>. Overall, leukocytes from Simmental compared with Holstein cows had greater expression of <i>IDO1</i>, <i>RPL13A</i>, <i>ALOX5</i>, <i>CD44</i>, <i>CX3CR1</i>, <i>ITGB2</i>, and <i>TNFA</i>, whereas expression of <i>CD16</i> and <i>TLR2</i> was lower. Overall, compared with multiparous cows, primiparous cows had higher expression of <i>IL1B</i>, <i>IL18</i>, <i>MYD88</i>, <i>SELL</i>, and <i>TLR2</i> and lower expression of <i>MMP9</i>. Simmental cows seemed more sensitive to induction of the immune system after calving, as revealed by the greater abundance of genes involved in immune system adaptation, regardless of pegbovigrastim treatment. Primiparous cows undergoing a new stress condition with respect to older cows were characterized by leukocytes with a higher inflammatory response. In conclusion, pegbovigrastim led to higher expression levels of most genes involved in the processes investigated, suggesting a thorough activation of the immune machinery during the critical post-partum period.
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spelling doaj.art-08de17e8d0c24abba35b9c0e8ddbd36d2023-11-19T20:40:17ZengMDPI AGAnimals2076-26152020-04-0110462110.3390/ani10040621Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental CowsVincenzo Lopreiato0Ernesto Palma1Andrea Minuti2Juan J. Loor3Mariangela Lopreiato4Francesca Trimboli5Valeria Maria Morittu6Anna Antonella Spina7Domenico Britti8Erminio Trevisi9Department of Animal Sciences, Food and Nutrition, Faculty of Agriculture, Food and Environmental Science, Università Cattolica del Sacro Cuore, 29122 Piacenza, ItalyInterdepartmental Services Centre of Veterinary for Human and Animal Health, Department of Health Science, Magna Græcia University, 88100 Catanzaro, ItalyDepartment of Animal Sciences, Food and Nutrition, Faculty of Agriculture, Food and Environmental Science, Università Cattolica del Sacro Cuore, 29122 Piacenza, ItalyDepartment of Animal Sciences and Division of Nutritional Sciences, University of Illinois, Urbana, IL 61801, USADepartment of Biochemical Sciences, Sapienza University of Rome, P.le A. Moro, 5, 00185 Rome, ItalyInterdepartmental Services Centre of Veterinary for Human and Animal Health, Department of Health Science, Magna Græcia University, 88100 Catanzaro, ItalyInterdepartmental Services Centre of Veterinary for Human and Animal Health, Department of Health Science, Magna Græcia University, 88100 Catanzaro, ItalyInterdepartmental Services Centre of Veterinary for Human and Animal Health, Department of Health Science, Magna Græcia University, 88100 Catanzaro, ItalyInterdepartmental Services Centre of Veterinary for Human and Animal Health, Department of Health Science, Magna Græcia University, 88100 Catanzaro, ItalyDepartment of Animal Sciences, Food and Nutrition, Faculty of Agriculture, Food and Environmental Science, Università Cattolica del Sacro Cuore, 29122 Piacenza, ItalyPegbovigrastim is a commercial long-acting analog of bovine granulocyte colony-stimulating factor (rbG-CSF) that promotes the increased count and functionality of polymorphonuclear cells in dairy cows around the time of parturition. We hypothesized that pegbovigrastim administered to periparturient cows at approximately seven days before parturition and within 24 hours after calving could affect the profiles of gene networks involved in leukocyte function. Blood was collected on Day 3 after calving from treated groups (pegbovigrastim (PEG); 13 Simmental (seven multiparous and six primiparous) and 13 Holstein (seven multiparous and six primiparous) cows) that received pegbovigrastim (Imrestor; Elanco Animal Health) and controls (CTR; 13 Simmental (seven multiparous and six primiparous) and 13 Holstein (six multiparous and seven primiparous) cows) that received saline solution. Blood from all cows was sampled from the jugular vein in a PAXgene Blood RNA System tube (Preanalytix, Hombrechtikon, Switzerland) for RNA extraction. The RT-qPCR analysis was performed to investigate a panel of 34 genes of interest, representing recognition, immune mediation, migration, cell adhesion, antimicrobial strategies, inflammatory cascade, oxidative pattern, and leukotrienes in whole blood leukocytes. Normalized data were subjected to the MIXED model of SAS (ver. 9.4) with treatment, breed, parity, and their interaction as fixed effects. Compared with CTR, whole blood leukocytes of PEG cows had higher expression of genes involved in recognition and immune modulation (<i>CD14</i>, <i>CD16</i>, <i>MYD88</i>, <i>TLR2</i>, and <i>TLR4</i>), cell adhesion (<i>ITGB2</i>, <i>ITGAL</i>, <i>TLN1</i>, <i>SELL</i>, <i>SELPLG</i>, and <i>CD44</i>), antimicrobial activity (<i>MMP9</i>, <i>LTF</i>, and <i>LCN2</i>), and inflammatory cascade (<i>CASP1</i>, <i>TNFRSF1A</i>, <i>IL1B</i>, <i>IL1R</i>, <i>IL18</i>, <i>IRAK1</i>, <i>NLRP3</i>, and <i>S100A8</i>). This suggested an improvement of migration, adhesion, and antimicrobial ability and an enhanced inflammatory response, which in turn could trigger immune cell activation and enhance function. Expression of <i>SOD2</i> and <i>ALOX5</i> was also greater in the PEG group. In contrast, compared with CTR cows, PEG led to lower expression of <i>RPL13A</i>, <i>ALOX15</i>, <i>IL8</i>, and <i>TNF</i>. Overall, leukocytes from Simmental compared with Holstein cows had greater expression of <i>IDO1</i>, <i>RPL13A</i>, <i>ALOX5</i>, <i>CD44</i>, <i>CX3CR1</i>, <i>ITGB2</i>, and <i>TNFA</i>, whereas expression of <i>CD16</i> and <i>TLR2</i> was lower. Overall, compared with multiparous cows, primiparous cows had higher expression of <i>IL1B</i>, <i>IL18</i>, <i>MYD88</i>, <i>SELL</i>, and <i>TLR2</i> and lower expression of <i>MMP9</i>. Simmental cows seemed more sensitive to induction of the immune system after calving, as revealed by the greater abundance of genes involved in immune system adaptation, regardless of pegbovigrastim treatment. Primiparous cows undergoing a new stress condition with respect to older cows were characterized by leukocytes with a higher inflammatory response. In conclusion, pegbovigrastim led to higher expression levels of most genes involved in the processes investigated, suggesting a thorough activation of the immune machinery during the critical post-partum period.https://www.mdpi.com/2076-2615/10/4/621pegbovigrastimSimmentaltransition periodPAXgenegene expressionimmune response
spellingShingle Vincenzo Lopreiato
Ernesto Palma
Andrea Minuti
Juan J. Loor
Mariangela Lopreiato
Francesca Trimboli
Valeria Maria Morittu
Anna Antonella Spina
Domenico Britti
Erminio Trevisi
Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows
Animals
pegbovigrastim
Simmental
transition period
PAXgene
gene expression
immune response
title Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows
title_full Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows
title_fullStr Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows
title_full_unstemmed Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows
title_short Pegbovigrastim Treatment around Parturition Enhances Postpartum Immune Response Gene Network Expression of whole Blood Leukocytes in Holstein and Simmental Cows
title_sort pegbovigrastim treatment around parturition enhances postpartum immune response gene network expression of whole blood leukocytes in holstein and simmental cows
topic pegbovigrastim
Simmental
transition period
PAXgene
gene expression
immune response
url https://www.mdpi.com/2076-2615/10/4/621
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