A1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä

Amine oxidase activity regulates the development of pulmonary fibrosis




Julkaisun tekijät: Marttila-Ichihara F, Elima K, Auvinen K, Veres TZ, Rantakari P, Weston C, Miyasaka M, Adams D, Jalkanen S, Salmi M

Kustantaja: FEDERATION AMER SOC EXP BIOL

Julkaisuvuosi: 2017

Journal: FASEB Journal

Tietokannassa oleva lehden nimi: FASEB JOURNAL

Lehden akronyymi: FASEB J

Volyymi: 31

Julkaisunumero: 6

Sivujen määrä: 15

ISSN: 0892-6638

eISSN: 1530-6860

DOI: http://dx.doi.org/10.1096/fj.201600935R


Tiivistelmä
In pulmonary fibrosis, an inflammatory reaction and differentiation of myofibroblasts culminate in pathologic deposition of collagen. Amine oxidase copper containing-3 (AOC3) is a cell-surface-expressed oxidase that regulates leukocyte extravasation. Here we analyzed the potential role of AOC3 using gene-modified and inhibitor-treatedmice in a bleomycin-induced pulmonary fibrosis model. Inflammation and fibrosis of lungswere assessed by histologic, flow cytometric, and quantitative PCR analysis. AOC3-deficient mice showed a 30-50% reduction in fibrosis, collagen synthesis, numbers ofmyofibroblasts, and accumulation of CD4(+) lymphocytes, NK T cells, macrophages, andtype 2 innate lymphoidcells compared with wild-type controlmice. AOC3-knock-inmice, which express a catalytically inactive form of AOC3, were also protected from lung fibrosis. In wild-type mice, a small-moleculeAOC3inhibitor treatment reduced leukocyte infiltration, myofibroblast differentiation, andfibrotic injury both in prophylactic and early therapeutic settings by about 50% but was unable to reverse the established fibrosis. AOC3 was also induced in myofibroblasts in human idiopathic pulmonary fibrosis. Thus, the oxidase activity of AOC3 contributes to the development of lung fibrosis mainly by regulating the accumulation of pathogenic leukocyte subtypes, which drive the fibrotic response.-Marttila-Ichihara, F., Elima, K., Auvinen, K., Veres, T. Z., Rantakari, P., Weston, C., Miyasaka, M., Adams, D., Jalkanen, S., Salmi, M. Amine oxidase activity regulates the development of pulmonary fibrosis.


Last updated on 2021-24-06 at 11:55