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Regulation von Interleukin-6 durch Lipopolysaccharid-Stimulation in kultivierten humanen Detrusormyozyten

Lipopolysaccharide-mediated regulation of interleukin-6 in cultured human detrusor smooth muscle cells

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J.N. und N.S. trugen gleichermaßen zu der präsentierten Arbeit bei.

Zusammenfassung

Hintergrund

Interleukin-6 (IL-6) Plasma und Urinwerte sind bei Neoplasien und inflammatorischen Erkrankungen erhöht. Ziel der Arbeiten ist die Aufklärung der Genregulation glattmuskulärer Zielgene über die verschiedenen IL-6-Signalwege in kultivierten humanen Detrusormyozyten.

Patienten und Methoden

Die Expression von IL-6 und IL-6R (gp80, gp130) wurde immunhistochemisch, mit RT-PCR und Western-Blot untersucht. Stimulationsexperimente mit LPS wurden an kultivierten glatten Muskelzellen aus Blasenbiopsien von 4 männlichen Tumorpatienten durchgeführt.

Ergebnisse

IL-6- und IL-6R-Expression wurde in Urothel, Lamina propria und Detrusor gefunden. Stimulation mit LPS führte zu einer zeitabhängigen Synthese und/oder Freisetzung von IL-6, IL-6R und STAT3.

Diskussion

Die Ergebnisse sprechen für einen Einfluss von IL-6 in der Harnblase. Detrusor und Urothel können als Quelle für erhöhte IL-6-Werte dienen. Die Aufklärung der durch IL-6 regulierten Gene könnte weitreichende Konsequenzen für die Therapie von Tumoren und chronischen Entzündungen des unteren Harntrakts haben.

Abstract

Background

Interleukin-6 (IL-6) is a pleiotropic cytokine which shows elevated plasma and urine levels in cancer and inflammatory diseases of the urinary tract. The aim of the study is to define IL-6 target gene regulation in cultivated human detrusor smooth muscle cells.

Patients and methods

The expression of IL-6 and IL-6R (gp80, gp130) was studied by confocal immunofluorescence, rtPCR and Western blotting. Lipopolysaccharide (LPS) stimulation experiments were conducted in smooth muscle cell cultures derived from bladder biopsies of four male tumor patients.

Results

IL-6 and IL-6R expression was found in urothelium, lamina propria and detrusor cells. LPS stimulation evoked a time-dependent synthesis and/or release of IL-6, IL-6R and STAT3.

Conclusions

Our results favor the notion that IL-6 can stimulate various cells of the human urinary bladder. Both detrusor cells and urothelium can serve as a source of elevated IL-6 levels. Finding genes regulated by IL-6 could be of great value for new therapeutical approaches in cancer and chronic inflammation of the lower urinary tract.

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Neuhaus, J., Schlichting, N., Oberbach, A. et al. Regulation von Interleukin-6 durch Lipopolysaccharid-Stimulation in kultivierten humanen Detrusormyozyten. Urologe 46, 1193–1197 (2007). https://doi.org/10.1007/s00120-007-1479-2

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  • DOI: https://doi.org/10.1007/s00120-007-1479-2

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