Abstract
Background: COPD is characterized by airway remodelling and impaired repair of the lung epithelium due to inflammation. High-molecular-weight (HMW)-Hyaluronan (HA), a glycosaminoglycan in the extracellular matrix secreted by fibroblasts, is considered beneficial for tissue repair. In COPD, HA metabolism shifts towards the synthesis of low-MW (LMW)-HA and/or increased breakdown of HMW-HA, which has been associated with pro-inflammatory responses. However, the underlying mechanism is unknown.
Hypothesis: IL1β, as an inflammatory trigger, alters HA metabolism in the local lung microenvironment, hindering epithelial repair and inducing remodelling.
Methods: MRC5 fibroblasts or primary bronchial epithelial cells (PBECs) in air-liquid interface cultures alone, or their co-culture, and airway organoids were treated with IL1β or LMW-HA during differentiation. HA-metabolism, pro-inflammatory cytokines, mesenchymal markers, remodelling markers, and anti-oxidants were measured via qPCR/ELISA.
Results: IL1β induced increased HA-production in all models. This was associated with increased expression of the HA degrading enzyme HYAL2, suggesting increased LMW-HA production. IL1β promoted the expression of pro-inflammatory cytokines in both PBECs and MRC5 cultures, while anti-oxidant expression was inhibited in MRC5s, and remodelling markers were upregulated in PBECs. This was mimicked by LMW-HA treatment. However, the effects of both stimuli were limited when cells were co-cultured.
Conclusion: Our results suggest HA metabolism is altered in both PBECs and MRC5s upon IL1β stimulation and is associated with impaired repair and remodelling, which was not observed when co-cultured.
Footnotes
Cite this article as ERJ Open Research 2022; 8: Suppl. 8, 139.
This article was presented at the 2022 ERS Lung Science Conference, in session “Poster Session 2”.
This is an ERS Lung Science Conference abstract. No full-text version is available. Further material to accompany this abstract may be available at www.ers-education.org (ERS member access only).
- Copyright ©the authors 2022