Corticosteroid administration reduces the concentration of hyaluronan in bronchoalveolar lavage in a murine model of eosinophilic airway inflammation

Ernst, Glenda; Lompardía, Silvina; Russo, R; Gentilini, Virginia; Venturiello, Stella M.; Galíndez, Fernando; Grynblat, Pedro; Hajos, Silvia E.

doi:10.1007/s00011-012-0530-y

Cited by 6 publications

(4 citation statements)

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“…Phosphodiesterase 3 inhibitor Milrinone decreases HAS3 expression and inhibits LPS-induced lung inflammation and lung injury in ventilated rats [133]. Furthermore, corticosteroids, such as betamethasone or budesonide, reduce the concentration of LMW-HA in BAL fluids by decreasing the expression of HAS, as well as the phosphorylation of ERK and Akt signaling in vivo [134].…”

Section: Lmw-ha Signaling Inhibitionmentioning

confidence: 99%

Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity

2022

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Hyaluronic acid (HA) is a major component of the extracellular matrix. It is synthesized by hyaluronan synthases (HAS) into high-molecular-weight chains (HMW-HA) that exhibit anti-inflammatory and immunomodulatory functions. In damaged, infected, and/or inflamed tissues, HMW-HA are degraded by hyaluronidases (HYAL) or reactive oxygen species (ROS) to give rise to low-molecular-weight HAs (LMW-HAs) that are potent pro-inflammatory molecules. Therefore, the size of HA regulates the balance of anti- or pro-inflammatory functions. The activities of HA depend also on its interactions with hyaladherins. HA synthesis, degradation, and activities through HA/receptors interactions define the hyaluronasome. In this review, a short overview of the role of high and low-molecular-weight HA polymers in the lungs is provided. The involvement of LMW-HA in pulmonary innate immunity via the activation of neutrophils, macrophages, dendritic cells, and epithelial cells is described to highlight LMW-HA as a therapeutic target in inflammatory respiratory diseases. Finally, the possibilities to counter LMW-HA’s deleterious effects in the lungs are discussed.

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Section: Lmw-ha Signaling Inhibitionmentioning

confidence: 99%

Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity

2022

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“…Migration was measured using a 24-transwell plate (8 µm pore size, BD FalconTM, USA) [23]. Briefly, cells (3 × 10 5 cells/ml) were added to the upper compartment.…”

Section: Chemotaxis Assaysmentioning

confidence: 99%

Increased Levels of Hyaluronic Acid in Bronchoalveolar Lavage from Patients with Interstitial Lung Diseases, Relationship with Lung Function and Inflammatory Cells Recruitment

Ernst¹,

Jancic²,

Santiago³

et al. 2014

MRI

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Purpose: Interstitial Lung Diseases (ILD) are characterized by inflammation and fibrosis. It described the role of hyaluronic acid (HA) as an immune-regulator. It is not known if HA contributes to the recruitment of inflammatory cells associated with ILD. If this hypothesis was correct, then concentrations of HA in bronchoalveolar lavage (BAL) should correlate with the severity of ILD. Methods: We collected BAL from 22 ILD patients and 15 control subjects. We determined HA and cytokine levels by ELISA. In vitro chemotaxis assays were performed by using a transwell system. Results: We found that ILD patients showed a significant increase in HA, IL-6 levels and the amount of cells in BAL compared to control subjects. We detected a significant positive correlation between HA and IL-6 levels (r = 0.53 and p < 0.001) and an inverse relationship between HA levels and diffusion capacity (r = −0.59, p < 0.01). In vitro, HA induced migration of macrophages and monocytes through a CD44-dependent process. BAL from patients with ILD stimulated macrophage migration and this was abrogated by hyaluronidase. Conclusions: Our results support the hypothesis that HA contributes to the recruitment of monocytes towards the alveolar space, leading to exacerbation of lung inflammation in ILD patients.

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“…Anti-inflammatory treatment with the corticosteroid dexamethasone results in lower mortality amongst hospitalized COVID-19 patients (9). Corticosteroids are known to be effective in reducing HA levels in other inflammatory syndromes (10, 11), thus, clearance of HA may be critical in disease resolution following COVID-19 (5).…”

Section: Introductionmentioning

confidence: 99%

“…Anti-inflammatory treatment with the corticosteroid dexamethasone results in lower mortality amongst hospitalized COVID-19 patients (12). Corticosteroids are known to be effective in reducing HA levels in other inflammatory syndromes (13, 14), thus, clearance of HA may be critical in disease resolution following COVID-19 (8). We recently found that severe COVID-19 is an important risk factor for impaired respiratory function, characterized by a decrease in diffusion capacity (DL CO ), 3-6 months after the infection (15).…”

Section: Introductionmentioning

confidence: 99%

Hyaluronan in COVID-19 morbidity, a bedside-to-bench approach to understand mechanisms and long-term consequences of hyaluronan

Hellman

Rosendal

Edin

et al. 2023

Preprint

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Rationale: High levels of hyaluronan in lungs and blood associate with COVID-19 severity. However, the effects on systemic hyaluronan concentrations and the mechanisms involved in the pathological overproduction of hyaluronan upon SARS-CoV-2 infection remain incompletely characterized. Objectives: To determine how hyaluronan levels in blood of COVID-19 patients change over time and investigate SARS-CoV-2 impact on hyaluronan metabolism along with the effect of corticosteroid treatment. Methods: The concentrations of hyaluronan were measured in blood plasma from patients with mild (WHO Clinical Progression Scale, WHO-CPS, 1-5) and severe COVID-19 (WHO-CPS 6-9), both during the acute and convalescent phases. Primary human bronchial epithelial cells isolated from healthy donors were differentiated into an in vitro 3D-lung model and used to study effects of SARS-CoV-2 infection and corticosteroids treatment on hyaluronan metabolism. Measurements and Main results: Compared to healthy controls, both patients with mild and severe COVID-19 showed elevated plasma hyaluronan concentrations, which increased with disease severity. A reduction was observed over time, but hyaluronan levels remained elevated for at least 12 weeks, especially in women. SARS-CoV-2 infection in the 3D-lung model showed upregulation of inflammatory genes, hyaluronan synthases and downregulation of hyaluronidases, which increased the overall hyaluronan concentration. Notably, several of these effects were counteracted by corticosteroid treatment. Conclusions: Overproduction of hyaluronan plays a role in the pathogenesis of COVID-19 and hyaluronan levels in blood remain elevated over time. The in vitro mechanism for the positive effects of corticosteroid treatment in COVID-19 suggests a combined action of reduced inflammation and counteraction of hyaluronan synthesis.

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Corticosteroid administration reduces the concentration of hyaluronan in bronchoalveolar lavage in a murine model of eosinophilic airway inflammation

Abstract: We conclude that corticosteroids prevent the increase in HA in BAL from Dp-challenged mice. This effect is associated with reduced expression of HAS and reduced phosphorylation of Akt and ERK in the lungs of challenged mice.

Cited by 6 publications

References 40 publications

Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity

Lung Hyaluronasome: Involvement of Low Molecular Weight Ha (Lmw-Ha) in Innate Immunity

Increased Levels of Hyaluronic Acid in Bronchoalveolar Lavage from Patients with Interstitial Lung Diseases, Relationship with Lung Function and Inflammatory Cells Recruitment

Hyaluronan in COVID-19 morbidity, a bedside-to-bench approach to understand mechanisms and long-term consequences of hyaluronan

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