Fig. 9: Schematic diagram of the mechanisms underlying TcpC-mediated inhibition of NETosis. | Nature Communications

Fig. 9: Schematic diagram of the mechanisms underlying TcpC-mediated inhibition of NETosis.

From: TcpC inhibits neutrophil extracellular trap formation by enhancing ubiquitination mediated degradation of peptidylarginine deiminase 4

Fig. 9

Upon stimulation of LPS and PMA, NADPH oxidase catalyzes the intracellular O2 to generate ROS. ROS activate downstream NETosis essential enzyme, such as MPO, NE, and PAD4. NEs digest nucleosomal histones and promote chromatin relaxation, which favors PAD4 to catalyze histone into citrullinated histone. Citrullination of histones causes chromatin entropic swelling and release of NETs. In case of TcpC-secreting UPEC infection, TcpC inhibits pathogen-induced NETosis via two mechanisms: (1) Inhibition of ROS production, and (2) Functioning as an E3 ubiquitin ligase that promotes PAD4 degradation through ubiquitin-proteasome pathway.

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