Pam3CSK4 and LTA-TLRs ligands associated with microdomains induce IL8 production in human adrenocortical cancer cells.

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.

• Authors: W Kanczkowski, H Morawietz, C G Ziegler, R H Funk, G Schmitz, K Zacharowski, C E Mohn, M Ehrhart-Bornstein, S R Bornstein
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 39 Issue 6 Pg. 457-60 (Jun 2007) ISSN: 0018-5043 [Print] Germany
• PMID: 17578764 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-8
• Ligands
• Lipopeptides
• Lipopolysaccharides
• Pam(3)CSK(4) peptide
• Peptides
• Teichoic Acids
• Toll-Like Receptors
• lipoteichoic acid

Topics

• Adrenal Cortex Neoplasms (etiology, immunology)
• Humans
• Interleukin-8 (biosynthesis, genetics)
• Ligands
• Lipopeptides
• Lipopolysaccharides (pharmacology)
• Peptides (pharmacology)
• Teichoic Acids (pharmacology)
• Toll-Like Receptors (genetics, physiology)