Transcriptional profiling of the LPS induced NF-kappaB response in macrophages

BACKGROUND: Exposure of macrophages to bacterial products such as lipopolysaccharide (LPS) results in activation of the NF-kappaB transcription factor, which orchestrates a gene expression programme that underpins the macrophage-dependent immune response. These changes include the induction or repression of a wide range of genes that regulate inflammation, cell proliferation, migration and cell survival. This process is tightly regulated and loss of control is associated with conditions such as septic shock, inflammatory diseases and cancer. To study this response, it is important to have in vitro model systems that reflect the behaviour of cells in vivo. In addition, it is necessary to understand the natural differences that can occur between individuals. In this report, we have investigated and compared the LPS response in macrophage derived cell lines and peripheral blood mononuclear cell (PBMC) derived macrophages. RESULTS: Gene expression profiles were determined following LPS treatment of THP-1 cells for 1 and 4 hours. LPS significantly induced or repressed 72 out of 465 genes selected as being known or putative NF-kappaB target genes, which exhibited 4 temporal patterns of expression. Results for 34 of these genes, including several genes not previously identified as LPS target genes, were validated using real time PCR. A high correlation between microarray and real time PCR data was found. Significantly, the LPS induced expression profile of THP-1 cells, as determined using real time PCR, was found to be very similar to that of human PBMC derived macrophages. Interestingly, some differences were observed in the LPS response between the two donor PBMC macrophage populations. Surprisingly, we found that the LPS response in U937 cells was dramatically different to both THP-1 and PBMC derived macrophages. CONCLUSION: This study revealed a dynamic and diverse transcriptional response to LPS in macrophages, involving both the induction and repression of gene expression in a time dependent manner. Moreover, we demonstrated that the LPS induced transcriptional response in the THP-1 cell line is very similar to primary PBMC derived macrophages. Therefore, THP-1 cells represent a good model system for studying the mechanisms of LPS and NF-kappaB dependent gene expression.

Individual differences in mental control predict involuntary musical imagery

The experience of earworms, a type of involuntary musical imagery, may reflect a systematic failure in mental control. This study focused on how individual differences in each of two factors, schizotypy, or “openness to experience”, and thought suppression might relate to the appearance of the involuntary musical image (earworm). Schizotypy, was measured by Raine’s schizotypal personality questionnaire (SPQ; Raine, 1991) and thought suppression was measured by the White Bear Suppression Inventory (WBSI; Wegner & Zanakos, 1994). Each was found to contribute independently to the overall experience of involuntary musical imagery. Schizotypy was correlated with the length and disruptiveness of earworms, the difficulty with which they were dismissed and the worry they caused, but was not correlated with the frequency of such intrusive imagery. In turn, schizotypy was predicted by suppression and intrusion components of WBSI. The WBSI is associated with the length, disruptiveness, difficulty dismissing and interference but not with the worry caused or the frequency of earworms. The assumption of “ownership” of earworms was also found to affect the extent to which the earworms were considered worrying. Multiple regression analysis showed that both schizotypy and the WBSI predicted the difficulty with which unwanted musical images were dismissed, but that the WBSI accounted for additional variance on top of that accounted for by schizotypy. Finally we consider how earworm management might relate to wider cognitive processes.