title: Therapeutic effects of evasin-1, a chemokine binding protein, in bleomycin-induced pulmonary fibrosis.
abstract: CC chemokines play an important role in the pathogenesis of idiopathic pulmonary fibrosis. Few studies have evaluated the efficacy of therapeutically targeting CC chemokines and their receptors during interstitial lung diseases. In the present study, the therapeutic effects of Evasin-1, a tick-derived chemokine-binding protein that has high affinity for CCL3/microphage inflammatory protein (MIP)-1α, was investigated in a murine model of bleomycin-induced lung fibrosis. CCL3/MIP-1α concentrations in lung homogenates increased significantly with time after bleomycin challenge, and this was accompanied by increased number of leukocytes and elevated levels of CCL2/monocyte chemoattractant protein (MCP)-1, CCL5/regulated upon activation, normal T cell expressed and secreted, TNF-α and transforming growth factor-β(1), and pulmonary fibrosis. Administration of evasin-1 on a preventive (from the day of bleomycin administration) or therapeutic (from Day 8 after bleomycin) schedule decreased number of leukocytes in the lung, reduced levels of TNF-α and transforming growth factor-β(1), and attenuated lung fibrosis. These protective effects were similar to those observed in CCL3/MIP-1α-deficient mice. In conclusion, targeting CCL3/MIP-1α by treatment with evasin-1 is beneficial in the context of bleomycin-induced lung injury, even when treatment is started after the fibrogenic insult. Mechanistically, evasin-1 treatment was associated with decreased recruitment of leukocytes and production of fibrogenic cytokines. Modulation of CCL3/MIP-1α function by evasin-1 could be useful for the treatment of idiopathic pulmonary fibrosis.
authors.affiliation: Laboratório de Imunofarmacologia, Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas-Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, CEP 30882-650-Pampulha, Belo Horizonte, MG, Brazil.
authors.forename: Remo C
authors.initials: RC
authors.lastname: Russo
authors.forename: Ana L
authors.initials: AL
authors.lastname: Alessandri
authors.forename: Cristiana C
authors.initials: CC
authors.lastname: Garcia
authors.forename: Barbara F
authors.initials: BF
authors.lastname: Cordeiro
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pinho
authors.forename: Geovanni D
authors.initials: GD
authors.lastname: Cassali
authors.forename: Amanda E I
authors.initials: AE
authors.lastname: Proudfoot
authors.forename: Mauro M
authors.initials: MM
authors.lastname: Teixeira
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects* / Q000494:pharmacology; D054405:Chemokine CCL3 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D019707:Receptors, Chemokine / Q000737:chemistry / Q000627:therapeutic use*; D048508:Rhipicephalus sanguineus / Q000737:chemistry; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology
chemical_list: D000903:Antibiotics, Antineoplastic; C496534:Ccl3 protein, mouse; D054405:Chemokine CCL3; C523601:Evasin-1, Rhipicephalus sanguineus; D019707:Receptors, Chemokine; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D001761:Bleomycin