Gallate Moiety of Catechin Is Essential for Inhibiting CCL2 Chemokine-Mediated Monocyte Recruitment

Abstract

Leukocyte recruitment witnesses an orchestrated complex formation between the chemokines and their molecular partners. CCL2 chemokine that regulates monocyte trafficking is a worthwhile system from the pharmaceutical perspective. In the current study, four major catechins (EC/EGC/ECG/EGCG) were assessed for their inhibitory potential against CCL2-regulated monocyte/macrophage recruitment. Interestingly, catechins with the gallate moiety (ECG/EGCG) could only attenuate the CCL2induced macrophage migration. These molecules specifically bound to CCL2 on a pocket comprising the N-terminal, β 0 -sheets, and β 3 -sheets, and the binding affinity of ECGC (K d = 22 ± 4 μM) is ∼4 times higher than that of the ECG complex (K d = 85 ± 6 μM). MD simulation analysis evidenced that the molecular specificity/stability of CCL2−catechin complexes is regulated by multiple factors, including stereospecificity, number of hydroxyl groups on the annular ring-B, the positioning of the carbonyl group, and the methylation of the galloyl ring. Further, a significant overlap on the binding surface of CCL2 for EGCG/ECG and receptor interactions as evidenced from NMR data provided the rationale for the observed inhibition of macrophage migration in response to EGCG/ECG binding. In summary, these galloylated epicatechins can be considered as potent protein−protein interaction (PPI) inhibitors that regulate CCL2-directed leukocyte recruitment for resolving inflammatory/immunomodulatory disorders.

Immunocompetent mouse models revealed that S100A4 + monocytes/macrophages facilitate long-term Zika virus infection in the testes

“…Monocyte/macrophage migration is promoted by monocyte/macrophage chemotactic factors (MCFs) [ 51-53 ]. Our results proved that ZIKV infection promoted the recruitment of S100A4 + monocytes/macrophages into the testes by upregulating the expression of CCL2 and CCL5.…”

Gallation and B-Ring Dihydroxylation Increase Green Tea Catechin Residence Time in Plasma by Differentially Affecting Tissue-Specific Trafficking: Compartmental Model of Catechin Kinetics in Healthy Adults

“…Evidence from numerous epidemiological studies suggests that the greater intake of green tea affords protection against diseases affecting multiple organs and organ systems, including the cardiovascular system, liver, gastrointestinal tract, adipose tissue, and bones and teeth [ 35 ]. Recent in vitro and preclinical studies also demonstrate differential bioactivities of individual catechins depending on the study endpoint [ 10 , 36 , 37 , 38 , 39 , 40 ]. For example, studies in vitro demonstrate the superior free radical scavenging activity of EGCG [ 13 ] followed by ECG, EGC, and EC [ 22 ], indicating that catechin bioactivity is predicted by the number of hydroxyl groups present [ 41 ].…”