Tumor necrosis factor α– and interleukin‐1β–dependent induction of CCL3 expression by nucleus pulposus cells promotes macrophage migration through CCR1

摘要: Objective To investigate tumor necrosis factor α (TNFα) and interleukin-1β (IL-1β) regulation of CCL3 expression in nucleus pulposus (NP) cells macrophage migration. Methods Quantitative reverse transcription–polymerase chain reaction immunohistochemistry were used to measure NP cells. Transfections determine the role NF-κB, CCAAT/enhancer binding protein (C/EBPβ), MAPK on cytokine-mediated promoter activity. The effect NP-conditioned medium migration was measured using a Transwell system. Results An increase activity observed after TNFα or IL-1β treatment. Treatment with NF-κB inhibitors abolished cytokines expression. inductive p65 C/EBPβ confirmed through gain-of-function loss-of-function studies. Notably, cotransfection p50 completely blocked cytokine- p65-dependent induction. In contrast, c-Rel RelB had little Lentiviral transduction short hairpin RNA for (shp65) shIKKβ significantly decreased TNFα-dependent Analysis degenerated human tissue samples showed that CCL3, but not CCL4, correlated positively grade degeneration. Importantly, treatment macrophages conditioned treated promoted their migration. Pretreatment an antagonist CCR1, primary receptor migration. Conclusion Our findings indicate modulate by controlling activation MAPK, signaling. CCL3–CCR1 axis may play important promoting infiltration degenerated, herniated discs.