Animal models of thyroid goiter demonstrated that increased expression of IGF-I may contribute to early goiter formation Phillips et al. On the other hand, upregulated antiapoptotic moleculars, such as FLIP, were also proved to be involved in thyroid goiter formation through preventing apoptotic destruction of thyroid.
Although some attention has focused on the effect of IGF-I on FLIP expression, little information is available about its signaling pathway in normal thyroid tissue and in cell lines. Peruzzi et al. In addition, concomitant upregulation of FLIP gene transcription occurred. This involvement may explain why IGF-I plays an important role in the formation of thyroid goiters by upregulating antiapoptotic proteins. Our observation provides valuable therapeutic information. However, potential involvement of other signaling pathways and the precise underlying mechanisms still need further investigation.
A Representative reverse-transcription PCR results. B Histogram of real-time PCR results. D Densitometric results from three experiments of Western blotting. GAPDH, glyceraldehydephosphate dehydrogenase. Citation: Journal of Molecular Endocrinology 38, 6; Results from three independent experiments are shown.
C Equal amounts of total protein were loaded and western blotting was performed to measure FLIP protein expression. A representative blot is shown. D Densitometric results from three experiments. They also found similar effects, although less pronounced in the absence of TLR4. These experiments show that Myd88 is an important molecule in atherosclerosis and highly affects atherosclerotic chemokine expression.
JCI - NF-κB: a key role in inflammatory diseases
Particularly, TLR signaling is becoming more of interest to the atherosclerosis field. CD40 is a member of the TNF receptor family and is expressed on different cell types in atherosclerosis. Surprisingly, direct data using CDdeficient animals are still lacking, and most studies have focused on modifying CD40L, either by using CD40L-deficient animals or administration of CD40L-inhibiting antibodies. These data show that the CD40—CD40L system is a proatherogenic signaling cascade that also highly affects plaque stability. A major characteristic of the larger lesions was the increase in necrosis in the absence of macrophage IKK2.
Analysis of lesion progression showed a more advanced plaque phenotype, with increased macrophage influx in early lesions in the IKK2-deleted group. The combination of these 2 effects may be the main cause of the observed increased atherosclerosis. Interestingly, A20 was identified recently as an atherosclerosis-susceptibility locus in a quantitative trait loci analysis. Adeficient mice develop severe inflammation and cachexia and die prematurely, and A20 was shown recently to have ubiquitinating and deubiquitinating activity for RIP1 and TRAF6.
Finally, p50 was also identified recently as an important factor in the progression of atherosclerosis and the prevention of inflammation in the lesion. Studies performed in mice deficient for p50 in the cells of the hematopoietic system resulted in reduced atherosclerosis, although the atherosclerotic lesions were more inflamed and contained more B and T lymphocytes.
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Subsequent zooming in on these specific pathways may yield novel ways to modify atherosclerosis development. Because of restriction in the number of references, we often refer to reviews. View PDF. Tools Add to favorites Download citations Track citations Permissions. Jump to. Menno P. Marten H. Hofker Marten H. You are viewing the most recent version of this article. Previous versions: February 24, Previous Version 1.
Abstract Atherosclerosis is an inflammatory disease, characterized by the accumulation of macrophage-derived foam cells in the vessel wall and accompanied by the production of a wide range of chemokines, cytokines, and growth factors. Download figure Download PowerPoint. Correspondence to Menno P.
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Methylation of NF-κB and its Role in Gene Regulation
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