Hydrogel-based delivery of Il-10 improves treatment of bleomycin-induced lung fibrosis in mice

Significance: Fibrosis is the endpoint of chronic disease in multiple organs, including the skin, heart, lungs, intestine, liver, and kidneys. Pathologic accumulation of fibrotic tissue results in a loss of structural integrity and function, with resultant increases in morbidity and mortality. Understanding the pathways governing fibrosis and identifying therapeutic targets within those pathways is necessary to develop novel antifibrotic therapies for fibrotic disease. Recent Advances: Given the connection between inflammation and fibrogenesis, Interleukin-10 (IL-10) has been a focus of potential antifibrotic therapies because of its well-known role as an anti-inflammatory mediator. Despite the apparent dissimilarity of diseases associated with fibrotic progression, pathways involving IL-10 appear to be a conserved molecular theme. More recently, many groups have worked to develop novel delivery tools for recombinant IL-10, such as hydrogels, and cellbased therapies, such as ex vivo activated macrophages, to directly or indirectly modulate IL-10 signaling. Critical Issues: Some efforts in this area, however, have been stymied by IL-10's pleiotropic and sometimes conflicting effects. A deeper, contextual understanding of IL-10 signaling and its interaction with effector cells, particularly immune cells, will be critical to future studies in the field. Future Directions: IL-10 is clearly a gatekeeper of fibrotic/antifibrotic signaling. The development of novel therapeutics and cell-based therapies that capitalize on targets within the IL-10 signaling pathway could have far-reaching implications for patients suffering from the consequences of organ fibrosis.

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“…4). 59 The limitation of these models, however, is that pulmonary fibrosis resolves when bleomycin administration stops, unlike in human disease.…”

Section: Pulmonary Fibrosismentioning

confidence: 99%

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

Steen

Wang

Balaji

et al. 2020

Advances in Wound Care

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“…Current transplantation and dialysis treatments do not address the underlying pathophysiology of renal fibrosis and CKD, nor do they take advantage of the kidneys' inherent capacity for postinjury cytoprotective and regenerative functions (7)(8)(9). Notably, we and others have shown that interleukin-10 (IL-10) and hyaluronan (HA) are critical for regenerative healing in most organs (10)(11)(12)(13). This means that elucidating innate mechanisms that regulate regenerative tissue repair could provide new knowledge that would lead to adjuvant treatments to reduce fibrosis and improve CKD patient outcomes and quality of life (14,15).…”

Section: Introductionmentioning

confidence: 99%

High–molecular weight hyaluronan attenuates tubulointerstitial scarring in kidney injury

Wang¹,

Balaji²,

Steen³

et al. 2020

JCI Insight

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“…The BLM-induced PF mouse model has similar inflammatory and fibrotic characteristics as human PF, and it is widely adopted to simulate the pathogenesis of PF [ 25 , 33 ]. The PF mouse model induced with BLM (MP Biomedicals, Shanghai, China) was performed as described before [ 33 ]. Briefly, 100 mice were randomly divided into five groups, with 20 animals per group: normal (untreated), BLM-treated group, and the EGb761-treated groups (low, medium, and high EGb761 dose).…”

Section: Methodsmentioning

confidence: 99%

Ginkgo biloba Extract EGb761 Attenuates Bleomycin-Induced Experimental Pulmonary Fibrosis in Mice by Regulating the Balance of M1/M2 Macrophages and Nuclear Factor Kappa B (NF-κB)-Mediated Cellular Apoptosis

Pan

et al. 2020

Med Sci Monit

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Background The aim of this study was to show whether the standardized Ginkgo biloba extract EGb761, a traditional Chinese medicine, has a therapeutic effect on pulmonary fibrosis (PF). Material/Methods Bleomycin (BLM) was used for establishing the PF mouse model. The mice were treated with a gradient of EGb761 for 28 days to determine an appropriate drug dose. On day 28, the effect of EGb761 on lung injury and inflammation was confirmed by hematoxylin and eosin and Masson staining and evaluated by pulmonary alveolitis and Ashcroft score. The balance of M1/M2 macrophages was evaluated with the respective markers inducible nitric oxide synthase and and interleukin-10 by real-time polymerase chain reaction. Furthermore, the expressions of fibrosis-associated protein α-smooth muscle actin (SMA), related inflammatory protein transforming growth factor (TGF)-β1, the apoptosis-related proteins B-cell lymphoma-associated X protein (Bax), B-cell lymphoma (Bcl)-2, caspase-3, caspase-9, and phosphorylated nuclear factor (NF)-κB (p65) were assessed by western blot. Results On day 28, PF was induced by treating with BLM, whereas EGb761 suppressed the PF of lung tissue. The BLM-induced imbalance of M1/M2 macrophages was reduced by EGb761. Furthermore, the increasing amounts of α-SMA and TGF-β1 induced by BLM were suppressed by EGb761. In addition, the protein or messenger ribonucleic acid expression levels of phosphorylated NF-κB (p65), caspase-3, and caspase-9 were upregulated, whereas Bax and Bcl-2 were downregulated. Treatment with EGb761 restored the levels of these proteins except for caspase-9. Conclusions This study illustrated the protective effect of EGb761 on BLM-induced PF by regulating the balance of M1/M2 macrophages and NF-κB (p65)-mediated apoptosis. The results demonstrated the potential clinical therapeutic effect of EGb761, providing a novel possibility for curing PF.

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Hydrogel-based delivery of Il-10 improves treatment of bleomycin-induced lung fibrosis in mice

Cited by 70 publications

References 54 publications

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

The Role of the Anti-Inflammatory Cytokine Interleukin-10 in Tissue Fibrosis

High–molecular weight hyaluronan attenuates tubulointerstitial scarring in kidney injury

Ginkgo biloba Extract EGb761 Attenuates Bleomycin-Induced Experimental Pulmonary Fibrosis in Mice by Regulating the Balance of M1/M2 Macrophages and Nuclear Factor Kappa B (NF-κB)-Mediated Cellular Apoptosis

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