Abstract
Objective: This paper is aimed at to evaluate B7-H1 expression as induced by human cytomegalovirus (HCMV) in extravillous cytotrophoblast cell line HPT-8 and possible underlying mechanism. Method: Real time PCR and flow cytometry were used to determine B7-H1 mRNA and protein before and after HCMV infection in HPT-8 cells. Western blot analysis was used to determine the level of MAPK phosphorylation in HPT-8 cell lines infected with HCMV. Results: 100TCID50 was found to be the most effective dose, capable of stimulating B7-H1 mRNA and protein expression in HPT-8 cells. When empty control group was considered to have a B7-H1 mRNA value of 1, B7-H1 mRNA was 4.32 in 100TCID50 group. In flow cytometry study, mean fluorescence intensity (MFI) of 100TCID50 group was 16.14, while empty control group was 1.34. Both mRNA and protein expression were found to be significantly increased (P<0.05) in 100TCID50 group compared to empty control group. The result of Western blot analysis showed increase in B7-H1 expression caused by the extracellular signaling that was related to ERK activation and the ERK inhibitor U0126 was found to reverse this increase. Conclusion: HCMV upregulates B7-H1 expression in human extravillous cytotrophoblast cell line HPT-8, which is related to MAPK activation. Our result would be helpful in finding better therapies against intrauterine HCMV infection.
Highlights
Maternal immunological tolerance of the fetal placenta involves the recognition of foreign antigens, especially, the paternally-inherited fetal antigens in such a way that does not induce an antifetal maternal immune response.[1]
Our results suggested human cytomegalovirus (HCMV) was a strong inducer of B7-H1 expression in extravillous cytotrophoblast cell line HPT-8, this might explain why HCMV was a common factor for intrauterine infection and might provide clues for future antiHCMV intrauterine infection strategy
Influence of HCMV infection on the phosphorylation of mitogen-activated protein kinase (MAPK) in HPT-8 cells: In order to determine possible mechanisms of HCMV induced B7-H1 expression in HPT-8 cells, we did Western-Blot to check the phosphorylation of MAPKs that could involved in the expression of B7-H1 mRNA
Summary
Maternal immunological tolerance of the fetal placenta involves the recognition of foreign antigens, especially, the paternally-inherited fetal antigens in such a way that does not induce an antifetal maternal immune response.[1]. Individual members of the B7 family can be both positive and negative regulators of the immune response depending on their specific counterreceptors.[2] B7-H1(PD-L1) is a negative regulator of the immune response in this family, which is important for formation and maintenance of maternal immunological tolerance of the fetal placenta.[2] It is a surface-bound ligand and it binds to the lymphocyte-expressed receptor, PD-1. This interaction inhibits antigen-specific activation and cytokine production by T cells. These studies have offered strong evidence that this pathway plays a role in tolerance to both self and foreign antigens
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