Endogenous annexin A1 counter-regulates bleomycin-induced lung fibrosis

Autor(es)

Damazo, Amilcar S. ^{[1, 2]} ; Sampaio, Andre L. F. ^{[3, 4]} ; Nakata, Cintia M. A. G. ^[2] ; Flower, Roderick J. ^[3] ; Perretti, Mauro ^[3] ; Oliani, Sonia M. ^[1]

Afiliação do(s) autor(es)

^[1] Sao Paulo State Univ UNESP, Dept Biol, Inst Biociencias Letras & Ciencias Exatas, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[2] Univ Fed Mato Grosso, Dept Basic Sci Hlth, Fac Med, BR-78060900 Cuiaba, MT - Brazil

^[3] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, London EC1M 6BQ - England

^[4] FarManguinhos FIOCRUZ, Dept Appl Pharmacol, BR-21041250 Rio De Janeiro - Brazil

• Tipo de documento: Artigo Científico
• Fonte: BMC IMMUNOLOGY; v. 12, OCT 19 2011.
• Citações Web of Science: 20

Resumo

Background: The balancing functions of pro/anti-inflammatory mediators of the complex innate responses have been investigated in a variety of experimental inflammatory settings. Annexin-A1 (AnxA1) is one mediator of endogenous anti-inflammation, affording regulation of leukocyte trafficking and activation in many contexts, yet its role in lung pathologies has been scarcely investigated, despite being highly expressed in lung cells. Here we have applied the bleomycin lung fibrosis model to AnxA1 null mice over a 21-day time-course, to monitor potential impact of this mediator on the control of the inflammatory and fibrotic phases. Results: Analyses in wild-type mice revealed strict spatial and temporal regulation of the Anxa1 gene, e. g. up-regulation in epithelial cells and infiltrated granulocytes at day 7, followed by augmented protein levels in alveolar macrophages by day 21. Absence of AnxA1 caused increases in: i) the degree of inflammation at day 7; and ii) indexes of fibrosis (assessed by deposition of hydroxyproline in the lung) at day 7 and 21. These alterations in AnxA1 null mice were paralleled by augmented TGF beta 1, IFN gamma and TNF alpha generation compared to wild-type mice. Finally, treatment of wild type animals with an AnxA1 peptido-mimetic, given prophylactically (from day 0 to 21) or therapeutically (from day 14 onward), ameliorated both signs of inflammation and fibrosis. Conclusion: Collectively these data reveal a pathophysiological relevance for endogenous AnxA1 in lung inflammation and, more importantly, fibrosis, and may open new insights for the pharmacological treatment of lung fibrosis. (AU)

• Processo FAPESP: 06/50015-0 - Efeito da proteina antiinflamatoria anexina 1 na fibrose pulmonar induzida pela bleomicina.
• Beneficiário: Amílcar Sabino Damazo
• Modalidade de apoio: Bolsas no Brasil - Jovens Pesquisadores
• Processo FAPESP: 05/56855-8 - Efeito da proteína antiinflamatória anexina 1 na fibrose pulmonar induzida pela bleomicina
• Beneficiário: Amílcar Sabino Damazo
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores