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

W. Kanczkowski; H. Morawietz; C. G. Ziegler; R. H. Funk; G. Schmitz; K. Zacharowski; C. E. Mohn; M. Ehrhart-Bornstein; S. R. Bornstein

doi:10.1055/s-2007-980189

Hormone and Metabolic Research, Table of Contents

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

Original

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

W. Kanczkowski¹ , H. Morawietz² , C. G. Ziegler¹ , R. H. Funk³ , G. Schmitz⁴ , K. Zacharowski⁵ , C. E. Mohn⁶ , M. Ehrhart-Bornstein¹ , S. R. Bornstein¹

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

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

Full Text

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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