Early Growth Response-1 Plays an Important Role in Ischemia-Reperfusion Injury in Lung Transplants by Regulating Polymorphonuclear Neutrophil Infiltration

Abstract

Both graft and recipient Egr-1 played a role in lung IRI, but the graft side contributed more 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.

Mechanisms of lung ischemia-reperfusion injury

“…Using wild-type or Egr-1−/− mice, Yamamoto et al . demonstrated that lung function after transplantation was most improved when donor and recipient animals were Egr-1 deficient, and graft function was intermittently improved when either the donor or recipient animal was Egr-1 deficient [27]. Graft function correlated inversely with neutrophil infiltration, and Egr-1 expression was detected in neutrophil cytoplasm.…”

“…methylene blue [36] or N-acetylcysteine [37]); 2) anti-inflammatory strategies using inhibitors of pro-inflammatory transcription factors (e.g. inhibitor of Egr-1 [27]) or inflammatory mediators (e.g. α1-antitrypsin [38*], anti-cytokine [11], or anti-HMGB1 [39] agents); 3) ventilation with gaseous molecules (e.g.…”

ATF3 inhibits the inflammation induced byMycoplasma pneumoniain vitro and in vivo

“…Egr‐1, a zinc‐finger transcription factor, represents an important pro‐inflammatory transcriptional regulator that mediates pro‐inflammatory responses in various cell types, including macrophages . In HEK293 cells, knockdown of Egr‐1 inhibited the LTC4‐induced IL‐8 expression and release, as well as resulting in the reduction of IL‐6, MCP‐1 and ICAM‐1 in lung transplants . Egr‐1 deficiency attenuates NF‐κB and TGF‐β mediated renal inflammation and fibrosis .…”

“…32 In HEK293 cells, knockdown of Egr-1 inhibited the LTC4induced IL-8 expression and release, 33 as well as resulting in the reduction of IL-6, MCP-1 and ICAM-1 in lung transplants. 34 Egr-1 deficiency attenuates NF-κB and TGF-β mediated renal inflammation and fibrosis. 35 These findings were consistent with our results…”

Minimizing Ischemia Reperfusion Injury in Xenotransplantation

“…In allotransplantation, there is now significant research on organ-specific mechanisms contributing to IRI, and IRIM strategies ( 23 , 24 , 40 , 41 , 66 , 165 , 227 ). Current research in IRIM for heart, lungs, kidney, and liver allografts include reducing the effects of ROS, and directly or indirectly inhibiting inflammatory mediators, complement, immune cell platelet adhesion and activation, and maintaining, preserving, or restoring endothelial barrier and vasoregulatory functions ( 23 , 41 , 50 , 52 , 114 , 190 , 227 – 265 ). Promising findings in reduction of lung IRI have included adenosine A2A receptor activation reducing microvascular permeability and lung injury, early growth response 1 (Egr1) deletion reducing neutrophil infiltration, C3a receptor antagonist decreasing cell injury and inflammation, carbon monoxide in cold flush reducing inflammatory mediators and cellular infiltrate, and nitric oxide to reduce pulmonary arterial pressures, inflammation, and apoptosis ( 50 , 52 , 190 , 266 – 269 ).…”