Inflammation is a host immune response against infectious, traumatic or autoimmune injury, normally leads to recovery. However if not properly controlled, inflammation can cause persistent tissue damage. Macrophage is a leukocyte that plays an important role in inflammation by detecting inducers and producing mediators. TLRs are a group of receptors that macrophage harbor to recognize PAMPs. TLR4 can be activated by LPS and embarks on a complex signaling cascade that leads to the transactivation of many inflammation and autoimmunity related genes. Arrestins are a group of scaffolding proteins that can desensitize 7TMR G protein signaling and also initiate signaling. Arrestin has been indicated to regulate non-7TMR receptor signaling including TLR4. Arrestin's function in TLR4 signaling in human macrophage was studied in this research using THP-1 cell model. THP-1 was induced to differentiate into macrophage by PMA. siRNA was applied to knock down arrestin 2 level. LPS was used to stimulate TLR4 signaling and relevant genes were measured by PCR array. The results showed that arrestin 2 level was increased during THP-1 differentiation and arrestin 2's regulation effects are different according to different gene groups. This research may provide novel insights on the mechanisms of inflammatory gene expression.
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