Identification of paraoxonase-1 in induced sputum from healthy volunteers

Umemoto, Yuichiro; Takata, Keiji; Hori, Masaharu; Sato, Keizo; Nakagawa, Kazuko

doi:10.1016/j.freeradbiomed.2008.12.005

Cited by 1 publication

(1 citation statement)

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“…The role of PON1 in lung disease remains largely unclear, although some studies have suggested a possible protective role in chronic obstructive lung disease, and inflammatory pulmonary disease related to mustard gas exposure [ 27 , 28 ]. The PON1 protein has been identified in non-ciliated bronchiolar epithelial cells (clara cells), which maintain the epithelium of the distal conducting airways of the lungs [ 29 ], and both the arylesterase activity and protein levels of PON1 have been identified in induced sputum from healthy volunteers [ 30 ]. In the work by Chen and colleagues, PON1 over-expression was protective in a murine model of asthma, decreasing bronchial wall thickness and fibrosis, and reducing inflammatory cells in bronchioalveolar lavage fluid [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

Suppressed paraoxonase-1 activity associates with elevated oxylipins and the presence of small airways disease in patients with rheumatoid arthritis

et al. 2022

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Background Rheumatoid arthritis (RA)-associated lung disease (LD) associates with significantly increased morbidity and mortality. Although oxidative stress plays an important role in the inflammatory responses in other forms of lung disease, minimal work has evaluated its role in RA-LD. The current work examines the relationship between the anti-oxidant HDL-associated enzyme paraoxonase-1 (PON1), the PON1 Q192R polymorphism, and a targeted oxylipin panel with RA-LD. Methods This study was conducted as a retrospective chart review of a longitudinal single-center cohort of 250 RA patients. CT scans of the chest were reviewed by the interpreting radiologist and classified as small airways disease (SAD), interstitial lung disease (ILD), and bronchiectasis. PON1 activity was measured by its lactonase, arylesterase, and paraoxonase functions. The PON1 Q192R polymorphism and a targeted lipidomics panel were performed as previously reported. Results 43.2% of the 250 RA patient cohort (n = 108) had available CT scans, including 48 patients (44.4%) with SAD, 27 patients (25.0%) with bronchiectasis, and 16 patients (14.8%) with ILD. Patients with SAD had significantly lower baseline PON1 activity by its arylesterase, and lactonase functions, as well as higher 15-HETE, LTB4, and PGE2 levels compared to those without SAD. These predictors of SAD remained significant after multivariate analysis including known risk factors for RA-LD. Suppressed PON1 activity also correlated with higher levels of 15-HETE and 12-HETE. Conclusion In a single-center RA cohort, suppressed baseline PON1 activity and elevation in the oxylipins 15-HETE, LTB4, and PGE2 predicted the presence of RA-SAD in longitudinal follow-up. Key Points• Small airways disease (SAD) was present in 44.4% of this rheumatoid arthritis (RA) cohort.• Patients with SAD had significantly lower baseline PON1 activity, as well as higher levels of the oxylipins 15-HETE, LTB4, and PGE2 levels compared to those without SAD.• Further work is warranted to confirm these findings and further define the role of PON1 and lipid oxidation in RA lung disease.

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