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Horm Metab Res 2007; 39(6): 457-460
DOI: 10.1055/s-2007-980189
Original

© Georg Thieme Verlag KG Stuttgart · New York

Pam3CSK4 and LTA-TLRs Ligands Associated with Microdomains Induce IL8 Production in Human Adrenocortical Cancer Cells

W. Kanczkowski 1 , H. Morawietz 2 , C. G. Ziegler 1 , R. H. Funk 3 , G. Schmitz 4 , K. Zacharowski 5 , C. E. Mohn 6 , M. Ehrhart-Bornstein 1 , S. R. Bornstein 1
  • 1Medical Clinic III, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany
  • 2Department of Vascular Endothelium and Microcirculation, Medical Faculty Carl Gustav Carus, University of Technology Dresden, Germany
  • 3Institute of Anatomy, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany
  • 4Institute for Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Germany
  • 5Molecular Cardio-protection and Inflammation Group, Department of Anaesthesia, University of Bristol, United Kingdom
  • 6Centro de Estudios Farmacologicos y Botanicos, Consejo Nacional de Investigaciones Cientificas y Tecnicas, Buenos Aires, Argentina
Further Information

Publication History

received 25.8.2006

accepted 27.11.2006

Publication Date:
18 June 2007 (online)

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Abstract

Bacterially derived ligands, Pam3CSK4 and LPS, can directly impact adrenal glands steroidogenesis through microdomain-related TLR1/2 and 4, respectively, and indirectly via immune cell-derived cytokines. The bilateral immunoadrenal relationship plays an important role in the proper functioning of both systems. CXC chemokine-dependent immune cell infiltration into adrenocortical carcinomas (ACC), which correlates with poor prognosis, is a common phenomenon. Recently, IL8 was identified in ACC and NCI-H295R cells, and was found to contribute to ACC tumour growth. The aim of this study was to clarify the role of different TLR ligands in IL8 production in NCI-H295R cells. This is the first study to demonstrate the expression of several TLRs including TLR1, 3, 6, 7 and 9 in human adrenocortical cells by using the RT-PCR approach. Only stimulation with TLR1/6 together with TLR2 ligands resulted in IL8 peptide and mRNA induction in a dose and time-dependent manner. Our data suggest that gram-positive bacteria-related TLR1/2/6 ligands might contribute to adrenal gland tumorigenesis via IL8 production.

Key words

Bacterial ligands - CXC chemokines - NCI-H295R - TLR1/2 - tumorigenesis - microdomains

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Correspondence

S. R. Bornstein

Department of Medicine

Carl Gustav Carus Medical School

University of Technology

01307 Dresden

Germany

Phone: +49/351/458 66 06

Fax: +49/351/458 63 36

Email: stefan.bornstein@uniklinikum-dresden.de