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ARS Home » Northeast Area » Beltsville, Maryland (BHNRC) » Beltsville Human Nutrition Research Center » Diet, Genomics and Immunology Laboratory » Research » Publications at this Location » Publication #339878
Title: Transcriptional and translational-uncoupling in regulation of the CXCL12 and its receptors CXCR4, 7 in THP-1 monocytes and macrophages

Author
item YU, LU - University Of Maryland
item Pham, Quynhchi
item YU, LIANGLI - University Of Maryland
item Wang, Thomas - Tom

Submitted to: Immunity, Inflammation and Disease Journal
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/16/2017
Publication Date: 3/1/2018
Citation: Yu, L., Pham, Q., Yu, L., Wang, T.T. 2018. Transcriptional and translational disconnect in regulation of the CXCL12 and its receptors CXCR4, 7 in THP-1 monocytes and macrophages. Immunity, Inflammation and Disease Journal. 6(1):106-116. https://doi.org/10.1002/iid3.199.
DOI: https://doi.org/10.1002/iid3.199

Interpretive Summary: The human immune system is complex and the regulation of immune responses remains to be fully elucidated. The chemokine CXCL12 and its receptors CXCR 4 and 7 play crucial roles in the immune system. In the present study, the 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. Differentiation did not affect the CXCR 4, 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 CXCR 4, 7 mRNA levels to a greater magnitude in d- than u-THP-1. LPS induction of CXCL12 protein was confirmed by ELISA and observing conditioned medium from LPS-treated macrophages increased migration of monocyte. Additionally, d-THP-1 having higher CXCR7 protein level was found not migrating towards CXCL12. In contrast, LPS did not affect CXCR4, 7 protein levels. Hence, this study indicated that CXCL12 and CXCR4, 7 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 a disconnect between transcriptional and translational regulation of CXCR4, 7 expressions by differentiation and TLR stimuli exist. This study provides novel information on regulatory mechanisms of immune responses that will benefit basic and translational scientists who are studying the regulation of immune responses.

Technical Abstract: The chemokine CXCL12 and its receptors, CXCR 4 and 7, play crucial roles in the immune system. In the present study, the 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. Differentiation did not affect the CXCR 4, 7 mRNA levels. Interestingly, the CXCL12 and CXCR7 proteins, but not CXCR4, were found to be up-regulated during differentiation. LPS, through the CD14-dependent pathway, induced CXCL12 and CXCR 4, 7 mRNA levels to a greater magnitude in d- than u-THP-1. LPS induction of CXCL12 protein was confirmed by ELISA and observing conditioned medium from LPS-treated macrophages increased migration of monocyte. Additionally, d-THP-1 having higher CXCR7 protein level was found not migrating towards CXCL12. In contrast, LPS did not affect CXCR4, 7 protein levels. Hence, this study indicated that CXCL12 and CXCR4, 7 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 a disconnect between transcriptional and translational regulation of CXCR4, 7 expressions by differentiation and TLR stimuli exist.