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Interferon-gamma stimulates neopterin release from cultured kidney epithelial cells
A Moutabarrik1, S Takahara, I Nakanishi
1Department of Urology, Osaka University Hospital, Japan.
Insights
Kidney epithelial cells (KEC) release neopterin, an immune system activation marker, when stimulated by interferon gamma (IFN-gamma). This finding suggests KEC contribute to elevated neopterin levels in kidney disease patients.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Neopterin is a key biomarker for immune system activation.
- Monocytes and macrophages are known producers of neopterin.
- The role of kidney epithelial cells (KEC) in neopterin production is less understood.
Purpose of the Study:
- To investigate the capacity of cultured KEC to secrete neopterin.
- To determine the specific stimuli that induce neopterin release from KEC.
Main Methods:
- Cultured KEC were exposed to various cytokines and mitogens, including interferon gamma (IFN-gamma), IL-1 beta, IL-2, IL-6, LPS, phorbol ester, and TNF-alpha.
- Neopterin release was measured in response to different stimuli in a dose- and time-dependent manner.
- Synergistic effects of TNF-alpha and IFN-gamma were evaluated.
Main Results:
- IFN-gamma significantly induced neopterin release from KEC in a dose- and time-dependent manner.
- Other tested cytokines and mitogens (IL-1 beta, IL-2, IL-6, LPS, phorbol ester) did not induce significant neopterin release.
- TNF-alpha alone induced minimal neopterin release but synergistically enhanced IFN-gamma-induced secretion.
Conclusions:
- KEC are capable of secreting neopterin, particularly when stimulated by IFN-gamma.
- KEC contribute to elevated serum or urine neopterin levels observed in conditions like kidney allograft rejection and infections.
- While KEC contribute to neopterin production, their overall contribution may be less significant than that of activated macrophages.
Abstract:
The ability of cultured kidney epithelial cells (KEC) to secrete neopterin, which is a marker of the activation of immune system was studied. In this study interferon gamma (IFN-gamma) was shown to induce neopterin release from KEC in a dose- and time-dependent manner. Many other cytokines and mitogens (IL-1 beta, IL-2, IL-6, LPS and phorbol ester) were tested for their ability to induce neopterin in KEC but all failed to induce a significant release of neopterin from KEC. By itself TNF-alpha induced a release of small amounts of neopterin but strongly potentiated the effect of IFN-gamma in a synergistic manner to induce neopterin secretion. These data indicate that not only monocytes and macrophages which it is well known secrete neopterin, but KEC are responsible also for the high serum or urine level of neopterin observed in patients with kidney allograft rejection or infections episodes. As the amount of neopterin released by KEC is smaller than that secreted by activated macrophages, the contribution of KEC to the overall production of neopterin during certain diseases may be small.
