Negative immunomodulatory effect of lipoxin receptor stimulating agent on macrophages infected by human cytomegalovirus

doi:10.3969/j.issn.2095-4344.2013.05.019

Abstract

Abstract:

BACKGROUND: Lipoxin can inhibit the synthesis of inflammatory cells, endothelial cells and mouse spleen dendritic cells into the cytokines, and it can also inhibit the biological effects of inflammatory cytokines on cells.
OBJECTIVE: To investigate the negative immunomodulatory effect of lipoxin receptor stimulating agent BML-111 on THP-1 macrophages infected by human cytomegalovirus.
METHODS: THP-1 derived macrophages were infected with human cytomegalovirus AD169 (multiplicity of infection=0.5), and the cultured cells were randomly divided into control group, human cytomegalovirus group and human cytomegalovirus+BML-111 group. Then the cell culture supernatant was collected at 0, 1, 2, 4, 12, 24, 48 and 72 hours after infection, and the expression levels of cytokines in each group were detected with enzyme-linked immunosorbent assay; mRNA levels of the factors were tested with real-time PCR; Western blot was used to detect the expression of p65 subunit protein in the nucleus after infection for 4 hours.
RESULTS AND CONCLUSION: Compared with the control group, the cytokine protein and mRNA expression both in human cytomegalovirus group and human cytomegalovirus+BML-111 group were increased significantly (P < 0.05). Compared with human cytomegalovirus group, the levels of interleukin-1β and tumor necrosis factor α in human cytomegalovirus+BML-111 group were decreased significantly, and thus the level of transforming growth factor-β was increased greatly (P < 0.05). There was no significant difference of the level of interleukin-10 between the two groups (P > 0.05) mRNA expression. mRNA expression of all the cytokines in human cytomegalovirus+BML-111 group was lower than that in human cytomegalovirus group (P < 0.05). Compared with the control group, the level of p65 subunit protein in the nucleus of human cytomegalovirus group and human cytomegalovirus+BML-111 group was increased significantly (P < 0.05). The level of p65 subunit protein in the nucleus of human cytomegalovirus+BML-111 group was lower than that of human cytomegalovirus group (P < 0.05). BML-111 may decrease the expression of interleukin-1β and tumor necrosis factor α, and promote the expression of transforming growth factor-β by inhibiting the nuclear translocation of nuclear factor-κB p65. Thus it plays negative immunoregulation effect on THP-1 macrophages infected by human cytomegalovirus.

Key words: organ transplantation, transplantation and immunology, cytomegalovirus, macrophages, lipoxin, lipoxin receptor stimulating agent, immunomodulatory, tumor necrosis factor, other grants-supported paper

CLC Number:

R318

Chen Xiao-hong, Shu Sai-nan, Liu Xing-lou, Wang Hui, Zhang Ju, Du Xiao-yi, Li Ge. Negative immunomodulatory effect of lipoxin receptor stimulating agent on macrophages infected by human cytomegalovirus[J]. Chinese Journal of Tissue Engineering Research, 2013, 17(5): 886-893.

Figures/Tables 9

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