Chemokine (C-X-C motif) ligand 9 (CXCL9) (74-103) is a C-terminal fragment of mature CXCL9.[1] It binds to the glycosaminoglycan heparin in a cell-free assay (Kd = 3.1 nM).[2] CXCL9 (74-103) inhibits the binding of CXCL8 or CXCL11 to heparin, as well as chemokine (C-C motif) ligand 2 (CCL2) binding to heparan sulfate, in a concentration-dependent manner.[1] Unlike full-length CXCL9, CXCL9 (74-103) does not increase intracellular calcium levels in CHO cells expressing human CXC receptor 3 (CXCR3). CXCL9 (74-103) reduces the cytopathogenic effect of respiratory syncytial virus (RSV) in HeLa cells, herpes simplex virus 1 (HSV-1) in human embryonic lung (HEL) cells, and dengue virus serotype 2 in HMEC-1 cells (EC50s = 23, 15, and 11 µM, respectively).[2] It inhibits CXCL8 (1-77)- or monosodium urate-induced neutrophil extravasation to the tibiofemoral articulation in mouse models of acute inflammation or gout, respectively, when administered at a dose of 100 µg/animal.[1] CXCL9 (74-103) increases survival and decreases liver neutrophil infiltration and necrosis in a mouse model of liver injury induced by acetaminophen .[3] Intravenous administration of CXCL9 (74-103) (100 µl of a 1 mg/ml solution) decreases bronchoalveolar lavage fluid (BALF) neutrophil infiltration and IL-1β levels, but does not reduce lung bacterial burden, in a mouse model of K. pneumoniae-induced pneumonia.[4]
References:
[1].Vanheule, V., Janssens, R., Boff, D., et al.The positively charged COOH-terminal glycosaminoglycan-binding CXCL9(74-103) peptide inhibits CXCL8-induced neutrophil extravasation and monosodium urate crystal-induced gout in miceJ. Biol. Chem.290(35)21292-21304(2015).
[2].Vanheule, V., Vervaeke, P., Mortier, A., et al.Basic chemokine-derived glycosaminoglycan binding peptides exert antiviral properties against dengue virus serotype 2, herpes simplex virus-1 and respiratory syncytial virusBiochem. Pharmacol.10073-85(2016).
[3].Marques, P.E., Vandendriessche, S., de Oliveira, T.H.C., et al.Inhibition of drug-induced liver injury in mice using a positively charged peptide that binds DNAHepatol. Commun.5(10)1737-1754(2021).
[4].Boff, D., Russo, R.C., Crijns, H., et al.The therapeutic treatment with the GAG-binding chemokine fragment CXCL9(74-103) attenuates neutrophilic inflammation and lung dysfunction during Klebsiella pneumoniae infection in miceInt. J. Mol. Sci.23(11)6246(2022).