Sequence similarities of a subgroup of CXC chemokines related to murine LIX: implications for the interpretation of evolutionary relationships among chemokines

Abstract

The murine CXC chemokine LIX has distinctive sequence features that suggest it is a novel chemokine. Among known human chemokines, ENA-78 and GCP-2 are the two most closely related to LIX. We have recently cloned the human GCP-2 gene. Phylogenetic analysis shows that the LIX coding region is more distant from both human GCP-2 and ENA-78 than is porcine AMCF-II, the chemokine with greatest sequence similarity to LIX. Human GCP-2 and ENA-78 have very high nucleotide similarity in non-coding as well as coding sequences, which suggests that these genes are the result of an evolutionarily recent gene duplication event. If this duplication occurred during primate evolution, then non-primate species may have only a single chemokine corresponding to this pair of human genes. This example shows that a one-to-one genetic correspondence does not necessarily exist between all the chemokine genes in two different species. These observations may have important implications for other chemokines that belong to clusters of closely related genes.

Resistance of Collagenase-2 (Matrix Metalloproteinase-8)-Deficient Mice to TNF-Induced Lethal Hepatitis

“…LIX is the only known murine PMN chemoattractant whose biological activity can be modulated by MMP-8, because MMP-8 generates truncated forms of LIX that are much more chemotactic than the full-length LIX (20). LIX is considered to be the murine counterpart of two closely related human chemokines, epithelial cell-derived neutrophil-activating peptide-78 and granulocyte chemotactic protein-2 (25).…”

Bacterial Clearance and Survival Are Dependent on CXC Chemokine Receptor-2 Ligands in a Murine Model of Pulmonary Nocardia asteroides Infection

“…Other intriguing ELR ϩ CXC chemokine candidates include LPS-induced CXC chemokine (LIX) and the recently described lungkine. LIX has significant structural homology with human epithelial neutrophilactivating protein-78 and granulocyte chemotactic protein-2 (37,38). During murine endotoxemia, prominent LIX expression was In contrast, anti-Ly-6G-treated lungs were devoid of any inflammatory cell influx (C).…”

The murine neutrophil-chemoattractant chemokines LIX, KC, and MIP-2 have distinct induction kinetics, tissue distributions, and tissue-specific sensitivities to glucocorticoid regulation in endotoxemia

“…Attempts to elucidate the individual roles of the seven human ELR ϩ CXC chemokines may benefit from insights provided in the murine system, even though a precise correspondence between individual murine and human ELR ϩ CXC chemokines may not exist [18]. Human NAP-2; GRO/MGSA-␣, -␤, -␥; ENA-78; and GCP-2 are all functional ligands for CXCR2 but not CXCR1 [12].…”

“…The two human chemokines most closely related to LIX are ENA-78 and GCP-2 [10,18]. The human ENA-78 and GCP-2 genes have very high sequence similarity and appear to be the result of an evolutionarily recent gene duplication [10].…”

“…The human ENA-78 and GCP-2 genes have very high sequence similarity and appear to be the result of an evolutionarily recent gene duplication [10]. LIX is equally closely related to both ENA-78 and GCP-2, and is not the murine ortholog of either gene [10,18]. The LIX cDNA encodes a predicted 92 amino acid mature peptide with a distinctive carboxyl-terminal region that extends 14 residues beyond the carboxyl-termini of other known ELR ϩ CXC chemokines.…”