TY - JOUR
T1 - iC3b-opsonized apoptotic cells mediate a distinct anti-inflammatory response and transcriptional NF-κB-dependent blockade
AU - Amarilyo, Gil
AU - Verbovetski, Inna
AU - Atallah, Mizhir
AU - Grau, Amir
AU - Wiser, Giora
AU - Gil, Oranit
AU - Ben-Neriah, Ynon
AU - Mevorach, Dror
PY - 2010/3
Y1 - 2010/3
N2 - In recent years, it has become apparent that the removal of apoptotic cells by macrophages and DC is not only noninflammatory, but also immune-inhibitory, in most although not all circumstances. Complement may be involved in the uptake of apoptotic cells via direct binding of bridging factors in some physiological circumstances, by opsonization and engagement of the complement receptors. In the current study, we use a complementdependent system of apoptotic cell clearance by human-derived macrophages and DC. Using a luciferase reporter gene and measuring immune response to non-opsonic zymosan, we show that iC3b-apoptotic cells induce NF-jB inhibition in response to zymosan and LPS at the nuclear translocation, transcriptional and post-transcriptional levels, leading to profound inhibition of proinflammatory cytokines. In addition, interaction with iC3b-opsonized apoptotic cells is characterized by macrophage secretion of IL-10 and lack of TGF-β secretion. In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct antiinflammatory response and transcriptional NF-κB-dependent blockage.
AB - In recent years, it has become apparent that the removal of apoptotic cells by macrophages and DC is not only noninflammatory, but also immune-inhibitory, in most although not all circumstances. Complement may be involved in the uptake of apoptotic cells via direct binding of bridging factors in some physiological circumstances, by opsonization and engagement of the complement receptors. In the current study, we use a complementdependent system of apoptotic cell clearance by human-derived macrophages and DC. Using a luciferase reporter gene and measuring immune response to non-opsonic zymosan, we show that iC3b-apoptotic cells induce NF-jB inhibition in response to zymosan and LPS at the nuclear translocation, transcriptional and post-transcriptional levels, leading to profound inhibition of proinflammatory cytokines. In addition, interaction with iC3b-opsonized apoptotic cells is characterized by macrophage secretion of IL-10 and lack of TGF-β secretion. In conclusion, in cells with iC3b receptors, opsonized apoptotic cells mediate a distinct antiinflammatory response and transcriptional NF-κB-dependent blockage.
KW - Apoptosis
KW - Complement
KW - NF-κB
KW - iC3b
UR - http://www.scopus.com/inward/record.url?scp=77749260603&partnerID=8YFLogxK
U2 - 10.1002/eji.200838951
DO - 10.1002/eji.200838951
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C2 - 20039295
AN - SCOPUS:77749260603
SN - 0014-2980
VL - 40
SP - 699
EP - 709
JO - European Journal of Immunology
JF - European Journal of Immunology
IS - 3
ER -