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

转录和翻译解偶联对 THP-1 单核细胞和巨噬细胞中 CXCL12 及其受体 CXCR4、7 的调节

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作者:Lu Yu, Liangli Yu, Quynhchi Pham, Thomas T Y Wang

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.

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.

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