%0 Journal Article
%T Chemokine N-terminal-derived peptides differentially regulate signaling by the receptors CCR1 and CCR5.
%A Larsen O
%A Schuermans S
%A Walser A
%A Louka S
%A Lillethorup IA
%A Våbenø J
%A Qvortrup K
%A Proost P
%A Rosenkilde MM
%J FEBS Lett
%V 597
%N 24
%D 2023 12 23
%M 37994578
%F 3.864
%R 10.1002/1873-3468.14778
%X Inflammatory chemokines are often elevated in disease settings, where the largest group of CC-chemokines are the macrophage inflammatory proteins (MIP), which are promiscuous for the receptors CCR1 and CCR5. MIP chemokines, such as CCL3 and CCL5 are processed at the N terminus, which influences signaling in a highly diverse manner. Here, we investigate the signaling capacity of peptides corresponding to truncated N termini. These 3-10-residue peptides displayed weak potency but, surprisingly, retained their signaling on CCR1. In contrast, none of the peptides generated a signal on CCR5, but a CCL3-derived tetrapeptide was a positive modulator boosting the signal of several chemokine variants on CCR5. In conclusion, chemokine N termini can be mimicked to produce small CCR1-selective agonists, as well as CCR5-selective modulators.