PMID- 29733455 OWN - NLM STAT- MEDLINE DCOM- 20190508 LR - 20190508 IS - 1938-3673 (Electronic) IS - 0741-5400 (Linking) VI - 104 IP - 2 DP - 2018 Aug TI - The chemokine fragment CXCL9(74-103) diminishes neutrophil recruitment and joint inflammation in antigen-induced arthritis. PG - 413-422 LID - 10.1002/JLB.3MA1217-502R [doi] AB - This study investigates if treatment with a peptide corresponding to the 30 C-terminal amino acids of CXCL9, CXCL9(74-103), ameliorates joint inflammation in a murine model of antigen-induced arthritis (AIA). AIA was induced in male C57BL/6J mice. Intravenous injection of CXCL9(74-103), simultaneously performed with a tibiofemoral challenge with methylated BSA (mBSA) as antigen in mice immunized with mBSA, diminished the accumulation of leukocytes, in particular neutrophils, in the synovial cavity. The levels of the chemokines CXCL1, CXCL2, and CXCL6 and of the cytokine IL-6 were decreased in inflamed periarticular tissue of mice treated with the CXCL9-derived peptide compared to non-treated AIA mice. In addition, CXCL9(74-103) treatment substantially reduced joint and cartilage damage. CXCL9(74-103) competes with CXCL6 and CCL3 for binding to the glycosaminoglycans heparan sulfate and chondroitin sulfate in vitro. In vivo, CXCL9(74-103) quickly binds to blood vessels in joints as observed by confocal microscopy. Next, we evaluated if later treatment with CXCL9(74-103) had a beneficial impact on joint inflammation. CXCL9(74-103) injection 6 h after mBSA challenge still reduced neutrophil accumulation in the joint, although it did not reduce chemokine and IL-6 concentrations. However, a delay of treatment until 12 h after challenge had no effect on cell recruitment and chemokine and IL-6 levels. Taken together, we demonstrated that treatment with a peptide, which interferes with the interaction between chemokines and glycosaminoglycans, from the beginning of the disease controlled the massive accumulation of neutrophils in the joint of AIA mice, greatly impacting on joint inflammation and tissue damage. CI - (c)2018 Society for Leukocyte Biology. FAU - Boff, Daiane AU - Boff D AD - Laboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium. AD - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Crijns, Helena AU - Crijns H AD - Laboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium. FAU - Janssens, Rik AU - Janssens R AD - Laboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium. FAU - Vanheule, Vincent AU - Vanheule V AD - Laboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium. FAU - Menezes, Gustavo B AU - Menezes GB AD - Centro de Biologia Gastrointestinal, Departamento de Morfologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Macari, Soraia AU - Macari S AD - Departmento de Clinica, Patologia e Cirurgias Odontologicas, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Silva, Tarcilia A AU - Silva TA AD - Departmento de Clinica, Patologia e Cirurgias Odontologicas, Faculdade de Odontologia, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Amaral, Flavio A AU - Amaral FA AD - Departamento de Bioquimica e Imunologia, Instituto de Ciencias Biologicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. FAU - Proost, Paul AU - Proost P AD - Laboratory of Molecular Immunology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180507 PL - England TA - J Leukoc Biol JT - Journal of leukocyte biology JID - 8405628 RN - 0 (Chemokine CXCL9) RN - 0 (Peptides) SB - IM MH - Animals MH - Arthritis, Experimental/*pathology MH - Arthritis, Rheumatoid/*pathology MH - Chemokine CXCL9/*pharmacology MH - Inflammation/pathology MH - Male MH - Mice MH - Mice, Inbred C57BL MH - Neutrophil Infiltration/*drug effects MH - Peptides/pharmacology OTO - NOTNLM OT - chondroitin sulfate OT - glycosaminoglycan OT - heparan sulfate OT - joint damage OT - proteoglycan EDAT- 2018/05/08 06:00 MHDA- 2019/05/09 06:00 CRDT- 2018/05/08 06:00 PHST- 2017/12/15 00:00 [received] PHST- 2018/03/01 00:00 [revised] PHST- 2018/04/05 00:00 [accepted] PHST- 2018/05/08 06:00 [pubmed] PHST- 2019/05/09 06:00 [medline] PHST- 2018/05/08 06:00 [entrez] AID - 10.1002/JLB.3MA1217-502R [doi] PST - ppublish SO - J Leukoc Biol. 2018 Aug;104(2):413-422. doi: 10.1002/JLB.3MA1217-502R. Epub 2018 May 7.