Inflammasomes in wound healing and fibrosis

Artlett, Carol M.

doi:10.1002/path.4116

Cited by 87 publications

(86 citation statements)

References 128 publications

(140 reference statements)

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“…Inflammasomes are multimolecular protein complexes responsible for caspase-1-driven activation of the pro-inflammatory cytokine interleukin (IL)-1β [9][10][11]. They are involved in the innate immunity by recognising pathogen-associated molecular patterns (PAMPs; on bacteria, viruses and fungi), and intracellular and extracellular damage-associated molecular patterns [9].…”

Section: Introductionmentioning

confidence: 99%

“…Alternatively, a recent report suggests that the NLRP3 inflammasome pathway is not linked to the severity of stable chronic obstructive pulmonary disease following analyses in the bronchoalveolar lavage fluid (BALF) and cellular components [21]. Recent evidence showing a possible activation of NLRP3 by cigarette smoking, another environmental risk factor for both IPF and rheumatoid arthritis, further supports the possible implication of inflammasomes in lung fibrosis [10,18]. The role of IL-1β has emerged in the pathogenesis of cigarette smoke-induced emphysema and small airway remodelling [22,23].…”

Section: Introductionmentioning

confidence: 99%

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NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

et al. 2016

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In this study we investigated the implication of NLRP3 inflammasomes in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and rheumatoid arthritis-usual interstitial pneumonia (RA-UIP).NLRP3 inflammasome activation at baseline and following stimulation with lipopolysaccharide/ATP was evaluated by measuring interleukin (IL)-1β and IL-18 levels released in the bronchoalveolar lavage fluid (BALF) fluid and by cultures of BALF cells. IL-1β and IL-18 levels were significantly elevated in the BALF and BALF macrophage cultures from RA-UIP patients, consistent with pre-existing inflammasome activation in these patients. In contrast, in IPF, BALF levels of IL-1β were significantly less elevated relative to RA-UIP and IL-18 was lower than controls. Furthermore, upon inflammasome stimulation, IPF BALF macrophage cultures failed to upregulate IL-1β and partly IL-18 secretion, in contrast to controls, which showed robust IL-1β and IL-18 upregulation. Interestingly, RA-UIP BALF cell cultures treated with lipopolysaccharide/ATP showed a potent stimulation of IL-18 secretion but not IL-1β, the latter being already elevated in the unstimulated cultures, while examination of the intracellular IL-1β levels in RA-UIP BALF cells upon NLRP3 inflammasome stimulation showed a significant upregulation of IL-1β suggesting the NLRP3 pathway could be further activated.Taken together, our results suggest distinct inflammasome activation profiles between autoimmune and idiopathic lung fibrosis. @ERSpublications Distinct NLRP3 inflammasome activation profiles between autoimmune and IPF lung macrophages compared with controls

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

et al. 2016

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“…Previous studies have demonstrated that reactive oxygen species (ROS) produced by hypertensive environments are important triggers of NLRP3 inflammasome activation. In addition, the NLRP3 inflammasome has been shown to be essential for the development and maintenance of inflammation during pulmonary fibrosis [11]. …”

Section: Introductionmentioning

confidence: 99%

Pirfenidone Attenuates Cardiac Fibrosis in a Mouse Model of TAC-Induced Left Ventricular Remodeling by Suppressing NLRP3 Inflammasome Formation

Wang¹,

Wu²,

Chen³

et al. 2013

Cardiology

127

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Objectives: Left ventricular remodeling is a frequent complication of hypertension with no therapeutic treatment available for the subsequent onset of myocardial fibrosis. Pirfenidone is an antifibrotic small-molecular-size drug with anti-inflammatory properties that is used as a treatment for fibrotic diseases, but its effects on hypertension-induced myocardial fibrosis are unknown. Therefore, we tested whether pirfenidone could ameliorate hypertension-induced left ventricular remodeling and whether hypertension-induced NLRP3 (Nod-like receptor pyrin domain containing 3), a critical protein in NLRP3 inflammasome formation, is involved in the therapeutic mechanism. Methods: A TAC-induced mouse model of hypertension and left ventricular hypertrophy was treated with pirfenidone, and survival, collagen deposition by histopathologic examination, heart function by echocardiography, concentrations of fibrosis-related inflammatory cytokines TGF-β₁, IL-1β in heart homogenate and in vitro cell cultures by ELISA, levels of ROS and inflammatory cells by flow cytometry, and levels of NLRP3 by Western blotting and immunohistochemistry were measured. Results: Pirfenidone increased the survival rate and attenuated myocardial fibrosis and inflammatory mediators in the TAC-induced hypertension-complicated left ventricular remodeling mouse model. The inhibition of NLRP3 expression by pirfenidone attenuated the expression of IL-1β and IL-1β-induced inflammatory and profibrotic responses. Conclusions: Pirfenidone may be useful in the treatment of hypertension-induced myocardial fibrosis by inhibiting NLRP3-induced inflammation and fibrosis.

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“…The hypoxic environment stimulates the expression of hypoxia-inducible factor 1α, which in turn induces downstream factors such as vascular endothelial growth factor (VEGF), SDF1α, platelet derived growth factor b8–12 and macrophage chemotactic protein 1 1 13 14. Cytokines stimulate the expression of cellular adhesion molecules such as integrins, and are capable of adhering to the ECM and endothelium adjacent to the damaged area 1–7 9 15–18.…”

Section: Signalling In Tissue Repair and Relevance To Tissue Engineeringmentioning

confidence: 99%

Combining tissue repair and tissue engineering; bioactivating implantable cell-free vascular scaffolds

Muylaert

Fledderus

Bouten

et al. 2014

Heart

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Synthetic replacement grafts for heart valves and small-diameter blood vessels such as coronary arteries have the potential to circumvent many of the limitations of currently available autologous grafting materials. Cell-free material incorporating biologically active compounds may guide the formation of fully autologous new tissue in situ derived from host cells after implantation. Inspiration for such bioactive compounds and their dynamics can be found in in vivo repair processes. Molecules such as stromal cell-derived factor 1α (SDF1α) that can attract progenitor cells from the bloodstream and modulate immune responses may be able to improve neotissue development in cell-free vascular and valvular grafts. Advances in the development of fully synthetic molecules and scaffold materials allow the spatial and temporal control of biologically active factors, enabling tissue engineers to mimic complex cellular signalling. This review focuses on combining knowledge of the molecular dynamics of factors involved in in vivo damage repair with the possibilities offered by newly developed synthetic materials. This approach has lead to encouraging results in the field of in situ vascular tissue engineering, and can ultimately lead to the development of off-the-shelf available vascular and valvular replacement grafts.

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Inflammasomes in wound healing and fibrosis

Cited by 87 publications

References 128 publications

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

NLRP3 inflammasome expression in idiopathic pulmonary fibrosis and rheumatoid lung

Pirfenidone Attenuates Cardiac Fibrosis in a Mouse Model of TAC-Induced Left Ventricular Remodeling by Suppressing NLRP3 Inflammasome Formation

Combining tissue repair and tissue engineering; bioactivating implantable cell-free vascular scaffolds

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