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Neuropathological changes in the PDAPP transgenic mouse model of Alzheimers disease
Abstracts / Toxicology Letters 172S (2007) S1–S240
I25 Analysis of IL-8 response in THP-1 cells following allergen stimulation Yuko Nukada, Masaaki Miyazawa, Yuichi Ito, Nanae Kosaka, Hitoshi Sakaguchi, Naohiro Nishiyama Kao Corporation, Tochigi, Japan Allergens induce the maturation of dendritic cells (DCs), including the up-regulation of cytokine production (TNF-alpha and IL-8, etc.) and surface molecules expression (CD86, CD54, etc.). MAPK signaling has also a crucial role in the maturation of DCs. Recently, we reported that allergens induced the maturation of THP-1 cells (a human monocytic leukemia cell line) as well as DCs. In our study, we investigated the role of IL-8 in the THP-1 cells response to allergen stimulation. We determined IL-8 production after stimulation of THP-1 cells with 22 chemicals, which have different potencies of sensitization. As a result, we observed a variety of allergens to predominantly induce IL-8 production like DCs. Next we investigated the role of MAPK signaling and TNF-alpha, which is known to have autocrine effect on DCs maturation, on IL-8 production. Treatment of THP-1 cells with both specific inhibitors for p38 MAPK (SB203580) and ERK (PD98059) suppressed the up-regulation of IL-8 production induced by DNCB, while only PD98059 suppressed IL-8 production induced by NiSO4. Neutralization of TNF-alpha activity, using specific antibody before stimulation with DNCB and NiSO4 , strongly suppressed IL-8 production. In conclusion, IL-8 production was predominantly induced in THP-1 cells following allergen stimulation. Furthermore, MAPK pathways (p38 and/or ERK) and TNF-alpha may be involved in the up-regulation of IL-8 production induced by DNCB and Ni in THP-1 cells. At present, the role of IL-8 produced by DCs in vivo is not clear. Further studies are expected. doi:10.1016/j.toxlet.2007.05.388 I26 Neuropathological changes in the PDAPP transgenic mouse model of Alzheimers disease Hamed Omidi 1 , Parichehr Pasbakhsh 2 , Kobra Mehrannia 2 , Ali Gholi Sobhani 2 1 Department
of Statistic, University of Alm, Farhang, Tehran, Iran; 2 Department of Anatomy, School of Medicine, Medical Sciences/University of Tehran, Tehran, Iran
S151
Alzheimers disease (AD) is a unique human disorder. Although the pathogenesis of AD is not fully understood, growing evidence indicates that the deposition of beta-amyloid (A) and the local reactions of various cell types to this protein play major roles in the development of the disease. In the present study transgenic mice expressing mutant amyloid precursor protein (APP) have been used. These mice exhibit selective neuronal death in the brain region that are most affected in AD, suggesting that amyloid plaque formation is directly involved in AD neurons loss. Brains from 12 transgenic animals and 12 age-matched non-transgenic littermate controls (1 and 2 years old) were examined histopathologically. One-year-old transgenic animals (n = 6) exhibit deposits of human A in the hippocampus, corpus callosum and cerebral cortex. By 2 years of age, a great number of diffuse and mature plaques were present in the cortex and hippocampus, and subcortical regions like thalamus and striatum. Another major finding was reduction of cholinergic cells in the medial septum, striatum and diagonal band of Broca. The present data are consistent with the hypothesis that the neuropathology begins in the cerebral cortex and hippocampus before spreading in a retrograde fashion to subcortical regions. doi:10.1016/j.toxlet.2007.05.389 I27 In vitro effects of iron oxide nanoparticles in human monocytic cells Jungsin Park 1,2,3,4,5 , Inhong Choi 1,2,3,4,5 , Jeonggi Lee 1,2,3,4,5 , Taegul Lee 1,2,3,4,5 , Daewon Moon 1,2,3,4,5 , Jinwoo Cheon 1,2,3,4,5 , Jinsil Choi 1,2,3,4,5 1 Yonsei
Medical University, Seoul, Republic of Korea; Korea 21, Seoul, Republic of Korea; 3 Nanomedical National Core Research Center, Seoul, Republic of Korea; 4 Chemistry Department of Yonsei University, Seoul, Republic of Korea; 5 Korea Research Institute of Standards and Science, Daejeon, Republic of Korea 2 Brain
Previous research shows that iron oxide cored nanoparticles are very useful MRI probes since the material is biocompatible and supplies more vivid images of the tissues and organs. In this paper, we investigated the influence of dimercaptosuccinic acid (DMSA) binded iron oxide nanoparticles (Fe3 O4 ) on human monocytic cell line, U937. The diameter of Fe3 O4 nanoparticles ranged from 20 to 200 nm measured by dynamic
I25 Analysis of IL-8 response in THP-1 cells following allergen stimulation Yuko Nukada, Masaaki Miyazawa, Yuichi Ito, Nanae Kosaka, Hitoshi Sakaguchi, Naohiro Nishiyama Kao Corporation, Tochigi, Japan Allergens induce the maturation of dendritic cells (DCs), including the up-regulation of cytokine production (TNF-alpha and IL-8, etc.) and surface molecules expression (CD86, CD54, etc.). MAPK signaling has also a crucial role in the maturation of DCs. Recently, we reported that allergens induced the maturation of THP-1 cells (a human monocytic leukemia cell line) as well as DCs. In our study, we investigated the role of IL-8 in the THP-1 cells response to allergen stimulation. We determined IL-8 production after stimulation of THP-1 cells with 22 chemicals, which have different potencies of sensitization. As a result, we observed a variety of allergens to predominantly induce IL-8 production like DCs. Next we investigated the role of MAPK signaling and TNF-alpha, which is known to have autocrine effect on DCs maturation, on IL-8 production. Treatment of THP-1 cells with both specific inhibitors for p38 MAPK (SB203580) and ERK (PD98059) suppressed the up-regulation of IL-8 production induced by DNCB, while only PD98059 suppressed IL-8 production induced by NiSO4. Neutralization of TNF-alpha activity, using specific antibody before stimulation with DNCB and NiSO4 , strongly suppressed IL-8 production. In conclusion, IL-8 production was predominantly induced in THP-1 cells following allergen stimulation. Furthermore, MAPK pathways (p38 and/or ERK) and TNF-alpha may be involved in the up-regulation of IL-8 production induced by DNCB and Ni in THP-1 cells. At present, the role of IL-8 produced by DCs in vivo is not clear. Further studies are expected. doi:10.1016/j.toxlet.2007.05.388 I26 Neuropathological changes in the PDAPP transgenic mouse model of Alzheimers disease Hamed Omidi 1 , Parichehr Pasbakhsh 2 , Kobra Mehrannia 2 , Ali Gholi Sobhani 2 1 Department
of Statistic, University of Alm, Farhang, Tehran, Iran; 2 Department of Anatomy, School of Medicine, Medical Sciences/University of Tehran, Tehran, Iran
S151
Alzheimers disease (AD) is a unique human disorder. Although the pathogenesis of AD is not fully understood, growing evidence indicates that the deposition of beta-amyloid (A) and the local reactions of various cell types to this protein play major roles in the development of the disease. In the present study transgenic mice expressing mutant amyloid precursor protein (APP) have been used. These mice exhibit selective neuronal death in the brain region that are most affected in AD, suggesting that amyloid plaque formation is directly involved in AD neurons loss. Brains from 12 transgenic animals and 12 age-matched non-transgenic littermate controls (1 and 2 years old) were examined histopathologically. One-year-old transgenic animals (n = 6) exhibit deposits of human A in the hippocampus, corpus callosum and cerebral cortex. By 2 years of age, a great number of diffuse and mature plaques were present in the cortex and hippocampus, and subcortical regions like thalamus and striatum. Another major finding was reduction of cholinergic cells in the medial septum, striatum and diagonal band of Broca. The present data are consistent with the hypothesis that the neuropathology begins in the cerebral cortex and hippocampus before spreading in a retrograde fashion to subcortical regions. doi:10.1016/j.toxlet.2007.05.389 I27 In vitro effects of iron oxide nanoparticles in human monocytic cells Jungsin Park 1,2,3,4,5 , Inhong Choi 1,2,3,4,5 , Jeonggi Lee 1,2,3,4,5 , Taegul Lee 1,2,3,4,5 , Daewon Moon 1,2,3,4,5 , Jinwoo Cheon 1,2,3,4,5 , Jinsil Choi 1,2,3,4,5 1 Yonsei
Medical University, Seoul, Republic of Korea; Korea 21, Seoul, Republic of Korea; 3 Nanomedical National Core Research Center, Seoul, Republic of Korea; 4 Chemistry Department of Yonsei University, Seoul, Republic of Korea; 5 Korea Research Institute of Standards and Science, Daejeon, Republic of Korea 2 Brain
Previous research shows that iron oxide cored nanoparticles are very useful MRI probes since the material is biocompatible and supplies more vivid images of the tissues and organs. In this paper, we investigated the influence of dimercaptosuccinic acid (DMSA) binded iron oxide nanoparticles (Fe3 O4 ) on human monocytic cell line, U937. The diameter of Fe3 O4 nanoparticles ranged from 20 to 200 nm measured by dynamic