Dual Roles of CD147 in Regulating THP-1 Monocyte Migration and MCP-1-Induced Inflammatory Responses

Cluster of Differentiation (CD) 147, a transmembrane glycoprotein, plays a critical role in monocyte function by regulating invasion, migration and cytokine production. This study explored the impact of CD147 on monocyte chemotaxis and inflammatory responses following monocyte chemoattractant protein-1 (MCP-1) modulation using CD147 knockout (CD147^KO) THP-1 monocytes. CD147^KO THP-1 cells exhibited significantly enhanced migration towards MCP-1 and chemoattractants secreted by MDA-MB-231 breast cancer cells compared to wild-type (WT) THP-1 cells, while surface expression of the adhesion molecule CD44 remained unchanged. Despite their increased migration, CD147^KO cells showed no significant differences in CC chemokine receptor type 1 (CC1) or CC chemokine receptor type 2 (CCR2) protein expression. Upon MCP-1 stimulation, CD147^KO THP-1 monocytes exhibited elevated mRNA expression of interleukin (IL)-6 and IL-10, accompanied by a reduction in tumor necrosis factor alpha (TNF-α) at higher MCP-1 concentrations. IL-6 upregulation in CD147^KO THP-1 monocytes appears to be a candidate mediator of their enhanced migratory capacity. In summary, this study highlights the dual role of CD147 as a potential checkpoint in regulating THP-1 monocyte migration, with its function varying depending on the context and microenvironment. Additionally, CD147^KO THP-1 monocytes exhibited a shift in the balance between pro- and anti-inflammatory cytokine responses.