M protein of group A streptococcus plays an essential role in inducing high expression of A20 that in turn down-regulates inflammatory responses
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摘要
Objective: Group A streptococcus(GAS), a common pathogen, resides in host for a long time by evading host immune attack. One of the underlying mechanisms is to upregulate the expression of immunosuppressive molecules and therefore reduces inflammatory cytokine production in immune cells. Here, we aim to explore the the mechanisms induced by GAS.Methods and Results: The proinflammatory cytokines expressed by macrophages were down-regulated following GAS stimulation through ELISA and Real time PCR. Interestingly, we observed that knocking-down A20 with shRNAincreased the expression of proinflammatory cytokines in macrophages in response to GAS stimulation. When macrophages were stimulated by M protein-mutant GAS, A20 expression was significantly decreased compared with that by WT GAS Moreover, the purified M protein induced high expression of A20 in macrophages. Conclusions: M protein plays an essential role in inducing high A20 expression in macrophages, which in turn downregulates inflammatory cytokine response. As a consequence of proinflammatory cytokine inhibition, appropriate immune responses were dampened to allow GAS survival in host.
Objective: Group A streptococcus(GAS), a common pathogen, resides in host for a long time by evading host immune attack. One of the underlying mechanisms is to upregulate the expression of immunosuppressive molecules and therefore reduces inflammatory cytokine production in immune cells. Here, we aim to explore the the mechanisms induced by GAS.Methods and Results: The proinflammatory cytokines expressed by macrophages were down-regulated following GAS stimulation through ELISA and Real time PCR. Interestingly, we observed that knocking-down A20 with sh RNAincreased the expression of proinflammatory cytokines in macrophages in response to GAS stimulation. When macrophages were stimulated by M protein-mutant GAS, A20 expression was significantly decreased compared with that by WT GAS Moreover, the purified M protein induced high expression of A20 in macrophages. Conclusions: M protein plays an essential role in inducing high A20 expression in macrophages, which in turn downregulates inflammatory cytokine response. As a consequence of proinflammatory cytokine inhibition, appropriate immune responses were dampened to allow GAS survival in host.
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