• Witold Mazur, Pamela Lindholm, Kirsi Vuorinen, Marjukka Myllärniemi, Kaisa Salmenkivi, and Vuokko L Kinnula.
• Department of Medicine, University of Helsinki, Helsinki University Hospital, Finland.
• APMIS. 2010 Sep 1; 118 (9): 703-12.

AbstractHuman idiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) have been proposed to be attributable to oxidative stress. The nuclear factor, erythroid derived 2, like protein (NRF2)-sulfiredoxin-1 (SRX1) pathway was hypothesized to be associated with the pathogenesis of human pulmonary fibrosis. Several methods including digital morphometry were used in the assessment of the cell-specific localization and expression of NRF2 and SRX1 and selected proteins linked to their activation/stability in human IPF/usual interstitial pneumonia (UIP) and NSIP lung. The proteins of the NRF2 pathway were localized in the hyperplastic alveolar epithelium and inflammatory cells in IPF and NSIP, but were absent in the fibroblastic foci characteristic of IPF. Morphometric evaluation revealed NRF2 and KEAP1 to be significantly elevated in the hyperplastic alveolar epithelium compared with the normal alveolar epithelium, and NRF2 was remarkably expressed in the nuclear compartment of the hyperplastic cells. SRX1 was expressed mainly in alveolar macrophages, and the number of SRX1-positive macrophages/surface area was elevated in NSIP, a disease which contains more marked inflammatory reaction compared with the IPF/UIP lung. The expression of the NRF2 pathway in human IPF and NSIP is further evidence that the pathogenesis of human fibrotic lung diseases is oxidant-mediated and originates from the alveolar epithelium.

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