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: Remo C Russo, Ana L Alessandri, Cristiana C Garcia, Barbara F Cordeiro, Vanessa Pinho, Geovanni D Cassali, Amanda E I Proudfoot, Mauro M Teixeira
• Journal: American journal of respiratory cell and molecular biology (Am J Respir Cell Mol Biol) Vol. 45 Issue 1 Pg. 72-80 (Jul 2011) ISSN: 1535-4989 [Electronic] United States
• PMID: 20833968 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antibiotics, Antineoplastic
• Ccl3 protein, mouse
• Chemokine CCL3
• Evasin-1, Rhipicephalus sanguineus
• Receptors, Chemokine
• Transforming Growth Factor beta
• Tumor Necrosis Factor-alpha
• Bleomycin

Topics

• Animals
• Antibiotics, Antineoplastic (administration & dosage, adverse effects)
• Bleomycin (adverse effects, pharmacology)
• Chemokine CCL3 (antagonists & inhibitors, genetics, immunology, metabolism)
• Disease Models, Animal
• Gene Expression Regulation (drug effects, immunology)
• Leukocytes (immunology, metabolism, pathology)
• Male
• Mice
• Mice, Knockout
• Pulmonary Fibrosis (chemically induced, drug therapy, immunology, metabolism, pathology)
• Receptors, Chemokine (chemistry, therapeutic use)
• Rhipicephalus sanguineus (chemistry)
• Transforming Growth Factor beta (biosynthesis, genetics, immunology)
• Tumor Necrosis Factor-alpha (biosynthesis, genetics, immunology)