ArticleAmerican journal of physiology. Lung cellular and molecular physiology2016
Human lung fibroblasts produce proresolving peroxisome proliferator-activated receptor-γ ligands in a cyclooxygenase-2-dependent manner.
Article in American journal of physiology. Lung cellular and molecular physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 20 citations in OpenAlex.
- Pulmonary hypertension: etiology and anti-inflammatory treatment pathways of natural products.Frontiers in pharmacology · 2025Review
- Is there a role for specialized pro-resolving mediators in pulmonary fibrosis?Pharmacology & therapeutics · 2023Review
- Neurotoxicity and neuroinflammatory effects of bisphenol A in male rats: the neuroprotective role of grape seed proanthocyanidins.Environmental science and pollution research international · 2022Article
- Article
- Carcinogenesis: Failure of resolution of inflammation?Pharmacology & therapeutics · 2021Review
- Fibroblast contributions to ischemic cardiac remodeling.Cellular signalling · 2021Review
- Therapeutic targeting of 15-PGDH in murine pulmonary fibrosis.Scientific reports · 2020Article
- Associations of Benzo(ghi)perylene and Heptachlorodibenzo-p-dioxin in Serum of Service Personnel Deployed to Balad, Iraq, and Bagram, Afghanistan Correlates With Perturbed Amino Acid Metabolism in Human Lung Fibroblasts.Journal of occupational and environmental medicine · 2019Article
- Exposure to Heptachlorodibenzo-p-dioxin (HpCDD) Regulates microRNA Expression in Human Lung Fibroblasts.Journal of occupational and environmental medicine · 2019Article
- Quenching the fires: Pro-resolving mediators, air pollution, and smoking.Pharmacology & therapeutics · 2019Review
- Prostaglandin EAmerican journal of physiology. Lung cellular and molecular physiology · 2019Article
- Activated Human Lung Fibroblasts Produce Extracellular Vesicles with Antifibrotic Prostaglandins.American journal of respiratory cell and molecular biology · 2019Article
- Activated human T lymphocytes inhibit TGFβ-induced fibroblast to myofibroblast differentiation via prostaglandins DAmerican journal of physiology. Lung cellular and molecular physiology · 2018Article
- Resolvin D1 Improves the Resolution of Inflammation via Activating NF-κB p50/p50-Mediated Cyclooxygenase-2 Expression in Acute Respiratory Distress Syndrome.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Human lung fibroblasts (HLFs) act as innate immune sentinel cells that amplify the inflammatory response to injurious stimuli. Here, we use targeted lipidomics to explore the hypothesis that HLFs also play an active role in the resolution of inflammation. We detected cyclooxygenase-2 (COX-2)-dependent production of both proinflammatory and proresolving prostaglandins (PGs) in conditioned culture medium from HLFs treated with a proinflammatory stimulus, IL-1β. Among the proresolving PGs in the HLF lipidome were several known ligands for peroxisome proliferator-activated receptor-γ (PPARγ), a transcription factor whose activation in the lung yields potent anti-inflammatory, antifibrotic, and proresolving effects. Next, we used a cell-based luciferase reporter to confirm the ability of HLF supernatants to activate PPARγ, demonstrating, for the first time, that primary HLFs activated with proinflammatory IL-1β or cigarette smoke extract produce functional PPARγ ligands; this phenomenon is temporally regulated, COX-2- and lipocalin-type PGD synthase-dependent, and enhanced by arachidonic acid supplementation. Finally, we used luciferase reporter assays to show that several of the PGs in the lipidome of activated HLFs independently activate PPARγ and/or inhibit NFκB. These results indicate that HLFs, as immune sentinels, regulate both proinflammatory and proresolving responses to injurious stimuli. This novel endogenous resolution pathway represents a new therapeutic target for globally important inflammatory diseases such as chronic obstructive pulmonary disease.
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