title: 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.affiliation: Medical Clinic III, Medical Faculty Carl Gustav Carus, University of Technology, Dresden, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Kanczkowski
authors.forename: H
authors.initials: H
authors.lastname: Morawietz
authors.forename: C G
authors.initials: CG
authors.lastname: Ziegler
authors.forename: R H
authors.initials: RH
authors.lastname: Funk
authors.forename: G
authors.initials: G
authors.lastname: Schmitz
authors.forename: K
authors.initials: K
authors.lastname: Zacharowski
authors.forename: C E
authors.initials: CE
authors.lastname: Mohn
authors.forename: M
authors.initials: M
authors.lastname: Ehrhart-Bornstein
authors.forename: S R
authors.initials: SR
authors.lastname: Bornstein
mesh_terms: D000306:Adrenal Cortex Neoplasms / Q000209:etiology / Q000276:immunology*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008024:Ligands; D055666:Lipopeptides; D008070:Lipopolysaccharides / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology*; D013682:Teichoic Acids / Q000494:pharmacology*; D051193:Toll-Like Receptors / Q000235:genetics / Q000502:physiology*
chemical_list: D016209:Interleukin-8; D008024:Ligands; D055666:Lipopeptides; D008070:Lipopolysaccharides; C508075:Pam(3)CSK(4) peptide; D010455:Peptides; D013682:Teichoic Acids; D051193:Toll-Like Receptors; C009900:lipoteichoic acid