Transcriptional and translational‐uncoupling in regulation of the CXCL12 and its receptors CXCR4, 7 in THP‐1 monocytes and macrophages

Abstract

Abstract Introduction The chemokine CXCL12 and its receptors CXCR4 and 7 play crucial roles in the immune system. In the present study, regulation of this pathway was further examined using the in‐vitro model of undifferentiated human THP‐1 monocytes (u‐THP‐1) and phorbol 12‐myristate 13‐acetate (PMA)‐differentiated THP‐1 macrophages (d‐THP‐1), to assess the effects of differentiation and the TLR4 ligand lipopolysaccharide (LPS) on the pathway. Methods/Results Differentiation did not affect the CXCR4, 7 mRNA levels. Interestingly, the CXCL12 and CXCR7 proteins but not CXCR4 were found to be up‐regulated during differentiation. LPS, through CD14‐dependent pathway, induced CXCL12 and CXCR4, 7 mRNA levels to a greater magnitude in d‐ than u‐THP‐1. The induction effect on CXCL12 stimulated by LPS was confirmed using ELISA. Increased migration of u‐THP‐1 was observed using conditioned medium from LPS‐treated d‐THP‐1. Additionally, d‐THP‐1, although expressed higher CXCR7 protein levels, failed to migrate toward CXCL12. In contrast, LPS did not affect CXCR4, 7 protein levels. Conclusion Hence, this study indicated that CXCL12, CXCR4, and CXCR7 were differentially expressed and regulated in u‐THP‐1 and d‐THP‐1 cells in response to external stimuli. Importantly, we reported here a novel observation that uncoupling exists between transcriptional and translational regulation of CXCR4, 7 expressions by differentiation and TLR stimuli.

Keywords

• CXCL12
• CXCR4
• CXCR7
• Lipopolysaccharide
• THP‐1