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Expression of cyclooxygenase-2 in biopsies obtained from human transplanted kidneys undergoing rejection
Birgit Hausknecht1, Stefanie Voelkl, Regine Riess
11 Medizinische Klinik IV, Universität Erlangen-Nürnberg, Erlangen, Germany.
Background:
The inducible cyclooxygenase (COX)-2 is a target of immunosuppressive drugs routinely administered to patients after transplantation. This study investigates a potential involvement of COX-2 in transplant rejection. Therefore, we examined the expression of COX-2 in biopsies obtained for diagnostic purposes.
Methods:
COX-2 was detected by immunohistochemistry and in situ hybridization. Congruent staining was obtained by both methods: in specimens of a kidney explanted as the result of vascular rejection, tubular epithelial cells and endothelial cells stained positively for COX-2. Furthermore, in appendiceal specimens obtained at surgery, epithelial cells of the crypts, interstitial cells, and mesothelial cells were positive by both methods, affirming the specificity of the antibody.
Results:
Compared with healthy control subjects, intensive staining of COX-2 was observed in most of the 28 biopsies obtained from patients diagnosed with vascular rejection combined with cellular interstitial rejection and tubulitis. Glomeruli and the macula densa area were essentially negative compared with prominent staining in cortical and medullary epithelial cells of the tubuli. Staining was distinct with individual positive cells in the tubular cross sections. Few arteries expressed COX-2 in intimal cells. Less prominent expression of COX-2 was detected in the biopsies of six kidneys obtained from patients diagnosed with acute tubular necrosis.
Conclusion:
This is the first report to show the up-regulation of COX-2 in human transplanted kidneys, despite ongoing immunosuppressive treatment. It remains to be established whether the up-regulation of COX-2 is part of the rejection process or has to be considered implicated in renal preservative mechanisms.
Insights
This study found increased cyclooxygenase-2 (COX-2) in human kidney transplants experiencing rejection, even with immunosuppression. Further research is needed to determine if COX-2 indicates rejection or aids kidney repair.
Area of Science:
- Immunology
- Nephrology
- Molecular Biology
Background:
- Inducible cyclooxygenase-2 (COX-2) is a target of immunosuppressive drugs used in transplant patients.
- The role of COX-2 in transplant rejection is not fully understood.
- This study aimed to investigate COX-2 expression in kidney transplant biopsies.
Purpose of the Study:
- To examine the expression of COX-2 in human transplanted kidneys.
- To determine if COX-2 is up-regulated during transplant rejection.
- To explore the potential role of COX-2 in the rejection process or renal preservation.
Main Methods:
- Immunohistochemistry and in situ hybridization were used to detect COX-2 expression.
- Biopsies from patients with diagnosed vascular rejection and controls were analyzed.
- Specificity of the COX-2 antibody was confirmed using appendiceal specimens.
Main Results:
- Intensive COX-2 staining was observed in most biopsies from patients with vascular rejection, cellular interstitial rejection, and tubulitis.
- COX-2 was prominently expressed in tubular epithelial cells and endothelial cells, but not in glomeruli or macula densa.
- Less prominent COX-2 expression was found in kidneys with acute tubular necrosis.
Conclusions:
- This is the first report demonstrating COX-2 up-regulation in human transplanted kidneys undergoing immunosuppressive treatment.
- The observed COX-2 up-regulation may be associated with the transplant rejection process.
- Further studies are required to elucidate whether COX-2 plays a role in renal preservative mechanisms.