Human lung cancer cells express functionally active Toll-like receptor 9

BACKGROUND: CpG-oligonucleotides (CpG-ODN), which induce signaling through Toll-like receptor 9 (TLR9), are currently under investigation as adjuvants in therapy against infections and cancer. CpG-ODN function as Th-1 adjuvants and are able to activate dendritic cells. In humans TLR9 has been described to be strongly expressed in B-lymphocytes, monocytes, plasmacytoid dendritic cells and at low levels in human respiratory cells. We determined whether a direct interaction of bacterial DNA with the tumor cells themselves is possible and investigated the expression and function of TLR9 in human malignant solid tumors and cell lines. TLR9 expression by malignant tumor cells, would affect treatment approaches using CpG-ODN on the one hand, and, on the other hand, provide additional novel information about the role of tumor cells in tumor-immunology. METHODS: The expression of TLR9 in HOPE-fixed non-small lung cancer, non-malignant tissue and tumor cell lines was assessed using immunohistochemistry, confocal microscopy, in situ hybridization, RT-PCR and DNA-sequencing. Apoptosis and chemokine expression was detected by FACS analysis and the Bio-Plex system. RESULTS: We found high TLR9 signal intensities in the cytoplasm of tumor cells in the majority of lung cancer specimens as well as in all tested tumor cell lines. In contrast to this non-malignant lung tissues showed only sporadically weak expression. Stimulation of HeLa and A549 cells with CpG-ODN induced secretion of monocyte chemoattractant protein-1 and reduction of spontaneous and tumor necrosis factor-alpha induced apoptosis. CONCLUSIONS: Here we show that TLR9 is expressed in a selection of human lung cancer tissues and various tumor cell lines. The expression of functionally active TLR9 in human malignant tumors might affect treatment approaches using CpG-ODN and shows that malignant cells can be regarded as active players in tumor-immunology

Entwicklung routinefaehiger Methoden fuer die molekularbiologische Tumordiagnostik Abschlussbericht

SIGLEAvailable from TIB Hannover: F01B445+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Bildung, Wissenschaft, Forschung und Technologie, Bonn (Germany)DEGerman

Neue Methoden der Genomanalyse. Teilprojekt 1: DNA-Polymerasen zum Einbau farbstoffmarkierter oder selbstfluoreszierender Nukleotide Abschlussbericht

Available from TIB Hannover: F99B1093+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Bildung und Forschung (BMBF), Bonn (Germany)DEGerman

Neuronal gene expression correlates of Parkinson's disease with dementia

Dementia is a common disabling complication in patients with Parkinson's disease (PD). The underlying molecular causes of Parkinson's disease with dementia (PDD) are poorly understood. To identify candidate genes and molecular pathways involved in PDD, we have performed whole genome expression profiling of susceptible cortical neuronal populations. Results show significant differences in expression of 162 genes (P < 0.01) between PD patients who are cognitively normal (PD-CogNL) and controls. In contrast, there were 556 genes (P < 0.01) significantly altered in PDD compared to either healthy controls or to PD-CogNL cases. These results are consistent with increased cortical pathology in PDD relative to PD-CogNL and identify underlying molecular changes associated with the increased pathology of PDD. Lastly, we have identified expression differences in 69 genes in PD cortical neurons that occur before the onset of dementia and that are exacerbated upon the development of dementia, suggesting that they may be relevant presymptomatic contributors to the onset of dementia in PD. These results provide new insights into the cortical molecular changes associated with PDD and provide a highly useful reference database for researchers interested in PDD