Expression of cyclooxygenase-1 and cyclooxygenase-2 in human renal allograft rejection - a prospective study

Abstract

Summary Cyclooxygenases (COX) are known to be involved in inflammatory kidney diseases. However, there are no data available about the expression of COX‐1 and only preliminary reports about the expression of COX‐2 in biopsies of patients undergoing acute renal allograft rejection. We conducted this prospective study to analyze the expression, distribution, and cellular localization of COX‐1 and ‐2 and thus to elucidate the role of COX in human kidney transplantation. One hundred forty‐four biopsies were included from patients without rejection and unaltered morphology (n = 60), with acute interstitial rejection (n = 7), with acute vascular rejection (n = 21), with chronic allograft nephropathy (n = 16), without rejection but with various other lesions (n = 40). COX‐1 and ‐2 expression was localized in each biopsy by immunohistochemistry. We found a highly significant up‐regulation of COX‐1 in vessels and in infiltrating interstitial cells of patients with acute allograft rejection compared with biopsies with well‐preserved tissue. Also, COX‐2 expression was significantly elevated in infiltrating interstitial cells of biopsies with acute rejection. This is the first prospective study demonstrating a significant induction of both COX‐1 and ‐2 in human allograft biopsies with acute rejection after renal transplantation.

Cyclooxygenase Expression and Platelet Function in Healthy Dogs Receiving Low‐Dose Aspirin

“…While cyclooxygenase function was inhibited by low‐dose aspirin as indicated by prolongation of PFA‐100 collagen/epinephrine closure times and decreased urine 11‐dTXB 2 concentrations, platelet expression of both COX‐1 and COX‐2 progressively increased throughout the course of aspirin administration. The COX‐1 enzyme isoform was originally thought to be strictly constitutively expressed, but recent studies have shown that COX‐1 expression can be induced in certain tissues, including human megakaryoblasts during thrombocytopoiesis . Similar to the results of this study, anti‐inflammatory doses of aspirin also cause increased platelet COX‐1 expression, decreased thromboxane synthesis, and inhibition in platelet function .…”

Implementation of an in vitro Model System for Investigation of Reperfusion Damage after Renal Ischemia

“…Due to our data, the increase in PGE 2 observed in our system is most likely due to in increase in COX-1. This is in accordance to an increase in COX-1 in tubular epithelial cells during human allograft rejection showing characteristics of AKI [34]. Interestingly, it is described that a substantial increase of NO (as is generated by iNOS) leads to reduced expression of COX-2 and an activation of COX-1 [40].…”

“…However, proximal tubular cells are thought not to express COX-2 in substantial quantities, although a basic expression of COX-2 [32] is described in these cells [33]. In human allograft rejection showing characteristics of AKI, COX-1 was described to be upregulated in tubular epithelial cells [34]. Therefore, we investigated the expression of both COX-2 and COX-1 during reperfusion.…”

Platelet Cyclooxygenase Expression in Normal Dogs

“…While it is generally believed that COX‐1 is constitutively expressed in most tissues, up‐regulation of COX‐1 expression has been demonstrated in human megakaryoblasts during thrombocytopoiesis, although the mechanism of enzyme up‐regulation is not fully understood . Up‐regulation of COX‐1 expression has also been identified in equine jejunal mucosa after periods of ischemia, in human gastric mucosa in association with gastric ulcers, and in humans experiencing rejection of a renal allograft . Certainly it appears that in some circumstances, cellular COX‐1 expression is induced rather than constitutive, and this study provides supportive evidence that suggests that exposure to aspirin induces COX‐1 expression by platelets or platelet precursors in dogs, although the mechanism for this induction remains unknown.…”