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Schook, Lawrence B. Ghildyal, Namit 2011-05-07T11:59:00Z 2011-05-07T11:59:00Z 10000-01-01 1990 CSF-1-induced bone marrow-derived macrophage (BMDM) differentiating in vitro acquire both antigen presenting and tumoricidal capabilities. In order to understand the molecular origin of macrophage diversity transcriptional and post-transcriptional regulation of genes involved in affector and effector functions were studied. Transcripts of c-fms and c-fos were detected at all stages of differentiation, whereas c-myc gene expression was highest during the proliferative stages of development. Endotoxin treatment of BMDM enhanced the expression of all proto-oncogenes, however the c-myc mRNA levels were highest on day 3 of culture. IFN-$\gamma$ treatment of BMDM cultures also enhanced the transcription of proto-oncogenes. Thus, it is felt that c-fms, c-fos and c-myc may be related to the complex mechanism of macrophage activation as evidenced by the stage-specific gene regulation. Interesting observations were made on the study of genes involved with functional state macrophage. Transcription of MHC class I and II genes occurred in the absence of any known Ia-inducing factor and the transcripts reached a maximum (3- to 4-fold) between days 5-7 of culture. IFN-$\gamma$ enhanced the transcription of both class I (2- to 5-fold) and II (2- to 10-fold) genes. Nuclear run-off assay results demonstrated that endotoxin treatment of the BMDM cultures augmented expression of both class I (2- to 3-fold) and II (2- to 3-fold) genes suggesting a post-transcriptional control of the MHC genes in the absence of an Ia-inducing factor. Upon endotoxin stimulation, transcription of IL-1$\alpha$ and IL-1$\beta$ showed almost similar kinetics which paralleled the kinetics of accumulation of steady state mRNA. This suggested that the expression of IL-1 genes are regulated transcriptionally. Tough both IFN-$\gamma$ and endotoxin enhanced (4- to 5-fold) the transcription of TNF-$\alpha$ gene, endotoxin had a more pronounced effect. The kinetics of TNF-$\alpha$ transcription paralleled the kinetics of steady state TNF-$\alpha$ mRNA accumulation, thereby suggesting both transcriptional and post-transcriptional control in the expression of TNF-$\alpha$ gene. Thus, these findings indicate that during macrophage development there is a sequential expression of immune system genes which is intrinsically determined. Made available in DSpace on 2011-05-07T11:59:00Z (GMT). No. of bitstreams: 2 license.txt: 4922 bytes, checksum: 910b249b4beec47e7ab768910c8f966f (MD5) 9021684.pdf: 4965694 bytes, checksum: cd499378cf5205d9b7d3fbf6a3143641 (MD5) Previous issue date: 1990 Item marked as restricted to the 'UIUC Users [automated]' Group (id=2) by Howard Ding (hding2@illinois.edu) on 2011-05-07T14:35:07Z Item is restricted indefinitely. Restriction data tranferred 2014-07-01T11:13:41-05:00 Original Data Group with Access UIUC Users [automated] Release Date: none Reason: ETDs are only available to UIUC Users without author permission ETDs are only available to UIUC Users without author permission U of I Only AAI9021684 (UMI)AAI9021684 http://hdl.handle.net/2142/19167 eng Copyright 1990 Ghildyal, Namit Biology, Molecular Health Sciences, Immunology Regulation of proto-oncogenes and immune system genes during CSF-1-induced macrophage differentiation text Animal Science Animal Science University of Illinois at Urbana-Champaign Dissertation Ph.D.