Early growth response-1 plays an important role in ischemia-reperfusion injury in lung transplants by regulating polymorphonuclear neutrophil infiltration

Sumiharu Yamamoto, Masaomi Yamane, Osamu Yoshida, Naohisa Waki, Mikio Okazaki, Akihiro Matsukawa, Takahiro Oto, Shinichiro Miyoshi

Research output: Contribution to journalArticle

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Abstract

Background. Early growth response-1 (Egr-1) has been shown to be a trigger-switch transcription factor that is involved in lung ischemia-reperfusion injury (IRI). Methods. Mouse lung transplants were performed in wild-type (WT) C57BL/6 and Egr1-knockout (KO) mice in the following donor→recipient combinations: WT→WT, KO→WT, WT→KO, and KO→KO to determine whether the presence of Egr-1 in the donor or recipient is the most critical factor for IRI. Pulmonary grafts were retrieved after 18 hours of ischemia after 4 hours of reperfusion. We analyzed graft function by analyzing arterial blood gas and histology in each combination and assessed the effects of Egr1 depletion on inflammatory cytokines that are regulated by Egr-1 as well on polymorphonuclear neutrophil (PMN) infiltration. Results. Deletion of Egr1 improved pulmonary graft function in the following order of donor→ recipient combinations: WT→ WT <WT→KO <KO→ WT <KO→ KO. Polymerase chain reaction assays for Il1B, Il6, Mcp1, Mip2, Icam1, and Cox2 showed significantly lower expression levels in the KO→KO group than in the other groups. Immunohistochemistry demonstrated clear Egr-1 expression in the nuclei of pulmonary artery endothelial cells andPMN cytoplasmin the WT grafts. Flow cytometry analysis showed that Egr1 deletion reduced PMN infiltration and that the extent of reduction correlatedwith graft function.Conclusions.Both graft and recipient Egr-1 played a role in lung IRI, but the graft side contributedmore to this phenomenon through regulation of PMN infiltration. Donor Egr-1 expression in pulmonary artery endothelial cells may play an important role in PMN infiltration, which results in IRI after lung transplantation.

Original languageEnglish
Pages (from-to)2285-2293
Number of pages9
JournalTransplantation
Volume99
Issue number11
DOIs
Publication statusPublished - Oct 23 2015

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Neutrophil Infiltration
Reperfusion Injury
Transplants
Lung
Growth
Pulmonary Artery
Endothelial Cells
Lung Transplantation
Knockout Mice
Reperfusion
Histology
Flow Cytometry
Transcription Factors
Ischemia
Gases
Immunohistochemistry
Cytokines
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Transplantation

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Early growth response-1 plays an important role in ischemia-reperfusion injury in lung transplants by regulating polymorphonuclear neutrophil infiltration. / Yamamoto, Sumiharu; Yamane, Masaomi; Yoshida, Osamu; Waki, Naohisa; Okazaki, Mikio; Matsukawa, Akihiro; Oto, Takahiro; Miyoshi, Shinichiro.

In: Transplantation, Vol. 99, No. 11, 23.10.2015, p. 2285-2293.

Research output: Contribution to journalArticle

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abstract = "Background. Early growth response-1 (Egr-1) has been shown to be a trigger-switch transcription factor that is involved in lung ischemia-reperfusion injury (IRI). Methods. Mouse lung transplants were performed in wild-type (WT) C57BL/6 and Egr1-knockout (KO) mice in the following donor→recipient combinations: WT→WT, KO→WT, WT→KO, and KO→KO to determine whether the presence of Egr-1 in the donor or recipient is the most critical factor for IRI. Pulmonary grafts were retrieved after 18 hours of ischemia after 4 hours of reperfusion. We analyzed graft function by analyzing arterial blood gas and histology in each combination and assessed the effects of Egr1 depletion on inflammatory cytokines that are regulated by Egr-1 as well on polymorphonuclear neutrophil (PMN) infiltration. Results. Deletion of Egr1 improved pulmonary graft function in the following order of donor→ recipient combinations: WT→ WT <WT→KO <KO→ WT <KO→ KO. Polymerase chain reaction assays for Il1B, Il6, Mcp1, Mip2, Icam1, and Cox2 showed significantly lower expression levels in the KO→KO group than in the other groups. Immunohistochemistry demonstrated clear Egr-1 expression in the nuclei of pulmonary artery endothelial cells andPMN cytoplasmin the WT grafts. Flow cytometry analysis showed that Egr1 deletion reduced PMN infiltration and that the extent of reduction correlatedwith graft function.Conclusions.Both graft and recipient Egr-1 played a role in lung IRI, but the graft side contributedmore to this phenomenon through regulation of PMN infiltration. Donor Egr-1 expression in pulmonary artery endothelial cells may play an important role in PMN infiltration, which results in IRI after lung transplantation.",
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T1 - Early growth response-1 plays an important role in ischemia-reperfusion injury in lung transplants by regulating polymorphonuclear neutrophil infiltration

AU - Yamamoto, Sumiharu

AU - Yamane, Masaomi

AU - Yoshida, Osamu

AU - Waki, Naohisa

AU - Okazaki, Mikio

AU - Matsukawa, Akihiro

AU - Oto, Takahiro

AU - Miyoshi, Shinichiro

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N2 - Background. Early growth response-1 (Egr-1) has been shown to be a trigger-switch transcription factor that is involved in lung ischemia-reperfusion injury (IRI). Methods. Mouse lung transplants were performed in wild-type (WT) C57BL/6 and Egr1-knockout (KO) mice in the following donor→recipient combinations: WT→WT, KO→WT, WT→KO, and KO→KO to determine whether the presence of Egr-1 in the donor or recipient is the most critical factor for IRI. Pulmonary grafts were retrieved after 18 hours of ischemia after 4 hours of reperfusion. We analyzed graft function by analyzing arterial blood gas and histology in each combination and assessed the effects of Egr1 depletion on inflammatory cytokines that are regulated by Egr-1 as well on polymorphonuclear neutrophil (PMN) infiltration. Results. Deletion of Egr1 improved pulmonary graft function in the following order of donor→ recipient combinations: WT→ WT <WT→KO <KO→ WT <KO→ KO. Polymerase chain reaction assays for Il1B, Il6, Mcp1, Mip2, Icam1, and Cox2 showed significantly lower expression levels in the KO→KO group than in the other groups. Immunohistochemistry demonstrated clear Egr-1 expression in the nuclei of pulmonary artery endothelial cells andPMN cytoplasmin the WT grafts. Flow cytometry analysis showed that Egr1 deletion reduced PMN infiltration and that the extent of reduction correlatedwith graft function.Conclusions.Both graft and recipient Egr-1 played a role in lung IRI, but the graft side contributedmore to this phenomenon through regulation of PMN infiltration. Donor Egr-1 expression in pulmonary artery endothelial cells may play an important role in PMN infiltration, which results in IRI after lung transplantation.

AB - Background. Early growth response-1 (Egr-1) has been shown to be a trigger-switch transcription factor that is involved in lung ischemia-reperfusion injury (IRI). Methods. Mouse lung transplants were performed in wild-type (WT) C57BL/6 and Egr1-knockout (KO) mice in the following donor→recipient combinations: WT→WT, KO→WT, WT→KO, and KO→KO to determine whether the presence of Egr-1 in the donor or recipient is the most critical factor for IRI. Pulmonary grafts were retrieved after 18 hours of ischemia after 4 hours of reperfusion. We analyzed graft function by analyzing arterial blood gas and histology in each combination and assessed the effects of Egr1 depletion on inflammatory cytokines that are regulated by Egr-1 as well on polymorphonuclear neutrophil (PMN) infiltration. Results. Deletion of Egr1 improved pulmonary graft function in the following order of donor→ recipient combinations: WT→ WT <WT→KO <KO→ WT <KO→ KO. Polymerase chain reaction assays for Il1B, Il6, Mcp1, Mip2, Icam1, and Cox2 showed significantly lower expression levels in the KO→KO group than in the other groups. Immunohistochemistry demonstrated clear Egr-1 expression in the nuclei of pulmonary artery endothelial cells andPMN cytoplasmin the WT grafts. Flow cytometry analysis showed that Egr1 deletion reduced PMN infiltration and that the extent of reduction correlatedwith graft function.Conclusions.Both graft and recipient Egr-1 played a role in lung IRI, but the graft side contributedmore to this phenomenon through regulation of PMN infiltration. Donor Egr-1 expression in pulmonary artery endothelial cells may play an important role in PMN infiltration, which results in IRI after lung transplantation.

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