论文部分内容阅读
Protease-Activated Receptors (PARs) are seven transmembrane domains that are activated by bacterial proteases as well as extracellular proteases like thrombin and neutrophil proteases,which are usually present during injury.However,little is known about the signaling pathways downstream of PAR activation.We have identified the key signaling molecules involved in the induction of innate immunity in human oral keratinocytes in response to PAR activation.Activation of PARs induces cell proliferation,expression of antimicrobial peptide human beta-defensin-2,and antimicrobial cytokines CXCL5/ENA-78 and CCL20/MIP3α.The ability of PARs to induce innate immune markers is linked to the transcription factor NF-κB.While PAR2 prominently sends signals via p38,both p38 and ERK MAP kinases are required for induction of innate immunity by PAR1.In addition,PI3K/Akt has a suppressing effect on the production of chemokines induced by PAR1/PAR2,and acts as a check to keep innate immune responses in balance.Our findings indicate that modulation of innate immunity by PARs may contribute to coordinated and balanced immuno-surveillance in the host.Induction of cytokines and chemokines by PAR activation leads to infiltration of mononuclear cells in the tissue.