title: Thymosin β4 reduces IL-17-producing cells and IL-17 expression, and protects lungs from damage in bleomycin-treated mice.
abstract: Thymosin β4 (Tβ4) is a highly conserved peptide with immunomodulatory properties. In this research we investigated the effects of Tβ4 on the bleomycin-induced lung damage in CD-1 mice and the changes in the number of IL-17-producing cells as well as the IL-17 expression in the lung. Male CD-1 mice were treated with bleomycin (1mg/kg) in the absence or the presence of Tβ4 (6mg/kg delivered intra-peritoneally on the day of bleomycin treatment and for 2 additional doses). After sacrifice one week later, lung histology, measurement of collagen content of the lung, Broncho Alveolar Lavage Fluid (BALF) analysis, evaluation of IL17-producing cells in the blood as well as RT-PCR and IHC in the lung tissue were performed. As expected, bleomycin-induced inflammation and lung damage were substantially reduced by Tβ4 treatment in CD-1 mice, as shown by the significant reduction of (i) leukocytes in BALF, (ii) histological evidence of the lung damage, and (iii) total collagen content in the lung. Importantly, the bleomycin-induced increase in the number of IL17-producing cells in the blood was significantly blocked by Tβ4. Accordingly, IHC and RT-PCR results demonstrated that Tβ4 substantially inhibited bleomycin-induced IL-17 over-expression in the lung tissue. This is the first report showing that a decreased amount of IL17-producing cells and inhibited IL-17 expression in the lung with Tβ4 treatment correlate with its anti-inflammatory and anti-fibrotic effects.
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Italy. Electronic address: econte@unict.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Conte
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Italy.
authors.forename: Maria
authors.initials: M
authors.lastname: Iemmolo
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Italy.
authors.forename: Evelina
authors.initials: E
authors.lastname: Fagone
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Gili
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Italy.
authors.forename: Mary
authors.initials: M
authors.lastname: Fruciano
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Genovese
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, University of Messina, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
authors.affiliation: Department of Clinical and Molecular Biomedicine, University of Catania, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Vancheri
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology / Q000633:toxicity; D001761:Bleomycin / Q000494:pharmacology / Q000633:toxicity*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D003094:Collagen / Q000032:analysis; D004195:Disease Models, Animal; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D020381:Interleukin-17 / Q000096:biosynthesis*; D007962:Leukocytes; D008168:Lung / Q000473:pathology; D055370:Lung Injury / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D008297:Male; D051379:Mice; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control*; D011897:Random Allocation; D013947:Thymosin / Q000494:pharmacology*; D000099201:Thymosin beta(4)
chemical_list: D000893:Anti-Inflammatory Agents; D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D003094:Collagen; D020381:Interleukin-17; D013947:Thymosin; D000099201:Thymosin beta(4)
keywords: Fibrosis; IL-17; IPF; Inflammation; Lung; Mice; Thymosin β4