PMID- 19277984
OWN - NLM
STAT- MEDLINE
DCOM- 20090514
LR  - 20220408
IS  - 1097-4652 (Electronic)
IS  - 0021-9541 (Linking)
VI  - 220
IP  - 1
DP  - 2009 Jul
TI  - Amyloid-beta up-regulates complement factor B in retinal pigment epithelial cells 
      through cytokines released from recruited macrophages/microglia: Another 
      mechanism of complement activation in age-related macular degeneration.
PG  - 119-28
LID - 10.1002/jcp.21742 [doi]
AB  - One of the earliest signs of age-related macular degeneration (AMD) is the 
      formation of drusen which are extracellular deposits beneath the retinal 
      pigmented epithelium (RPE). To investigate the relationship between drusen and 
      AMD, we focused on amyloid beta (Abeta), a major component of drusen and also of 
      senile plaques in the brain of Alzheimer's patients. We previously reported that 
      Abeta was accumulated in drusen-like structure in senescent neprilysin 
      gene-disrupted mice. The purpose of this study was to investigate the influence 
      of Abeta on factor B, the main activator of the complement alternative pathway. 
      The results showed that Abeta did not directly modulate factor B expression in 
      RPE cells, but increased the production of monocyte chemoattractant protein-1 
      (MCP-1). Abeta also increased the production of IL-1beta and TNF-alpha in 
      macrophages/microglia, and exposure of RPE cells to IL-1beta and TNF-alpha 
      significantly up-regulated factor B. Co-cultures of RPE cells and 
      macrophages/microglia in the presence of Abeta significantly increased the 
      expression of factor B in RPE. These findings indicate that cytokines produced by 
      macrophages/microglia that were recruited by MCP-1 produced in RPE cells 
      stimulated by Abeta up-regulate factor B in RPE cells. Thus, a combined mechanism 
      exists for Abeta-induced for the activation of the complement alternative pathway 
      in the subretinal space; cytokine-induced up-regulation of activator factor B and 
      dysfunction of the inhibitor factor I by direct binding to Abeta as suggested in 
      our earlier study.
FAU - Wang, Jiying
AU  - Wang J
AD  - Department of Ophthalmology and Visual Science, Tokyo Medical and Dental 
      University, Tokyo, Japan.
FAU - Ohno-Matsui, Kyoko
AU  - Ohno-Matsui K
FAU - Yoshida, Takeshi
AU  - Yoshida T
FAU - Shimada, Noriaki
AU  - Shimada N
FAU - Ichinose, Shizuko
AU  - Ichinose S
FAU - Sato, Tetsuji
AU  - Sato T
FAU - Mochizuki, Manabu
AU  - Mochizuki M
FAU - Morita, Ikuo
AU  - Morita I
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Physiol
JT  - Journal of cellular physiology
JID - 0050222
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Cytokines)
RN  - 0 (Interleukin-1beta)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 82115-62-6 (Interferon-gamma)
RN  - EC 3.4.21.47 (Complement Factor B)
RN  - EC 3.4.24.11 (Neprilysin)
SB  - IM
MH  - Amyloid beta-Peptides/*metabolism
MH  - Animals
MH  - Autocrine Communication
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Coculture Techniques
MH  - *Complement Activation
MH  - Complement Factor B/genetics/*metabolism
MH  - Cytokines/*metabolism
MH  - Epithelial Cells/*immunology
MH  - Humans
MH  - Interferon-gamma/metabolism
MH  - Interleukin-1beta/metabolism
MH  - Macrophages, Peritoneal/*immunology
MH  - Macular Degeneration/*immunology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microglia/*immunology
MH  - Neprilysin/deficiency/genetics
MH  - Paracrine Communication
MH  - Peptide Fragments/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Retinal Drusen/immunology
MH  - Retinal Pigment Epithelium/*immunology
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Up-Regulation
EDAT- 2009/03/12 09:00
MHDA- 2009/05/15 09:00
CRDT- 2009/03/12 09:00
PHST- 2009/03/12 09:00 [entrez]
PHST- 2009/03/12 09:00 [pubmed]
PHST- 2009/05/15 09:00 [medline]
AID - 10.1002/jcp.21742 [doi]
PST - ppublish
SO  - J Cell Physiol. 2009 Jul;220(1):119-28. doi: 10.1002/jcp.21742.