Browse
Submit Data
Databases
API
Help

Dataset Information

16 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

IL-13 is a therapeutic target in radiation lung injury.

ABSTRACT: Pulmonary fibrosis is a potentially lethal late adverse event of thoracic irradiation. Prior research indicates that unrestrained TGF-β1 and/or type 2 cytokine-driven immune responses promote fibrosis following radiation injury, but the full spectrum of factors governing this pathology remains unclear. Interleukin 13 (IL-13) is a key factor in fibrotic disease associated with helminth infection, but it is unclear whether it plays a similar role in radiation-induced lung fibrosis. Using a mouse model, we tested the hypothesis that IL-13 drives the progression of radiation-induced pulmonary fibrosis. Irradiated lungs from wild-type c57BL/6NcR mice accumulated alternatively-activated macrophages, displayed elevated levels of IL-13, and extensive fibrosis, whereas IL-13 deficient mice were resistant to these changes. Furthermore, plasma from irradiated wild-type mice showed a transient increase in the IL-13 saturated fraction of the circulating decoy receptor IL-13Rα2. Finally, we determined that therapeutic neutralization of IL-13, during the period of IL-13Rα2 saturation was sufficient to protect mice from lung fibrosis. Taken together, our results demonstrate that IL-13 is a major regulator of radiation-induced lung injury and demonstrates that strategies focusing on IL-13 may be useful in screening for timely delivery of anti-IL-13 therapeutics.

SUBMITTER: Chung SI

PROVIDER: S-EPMC5177927 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

IL-33-mediated IL-13 secretion by ST2+ Tregs controls inflammation after lung injury.

Project description:Acute respiratory distress syndrome is an often fatal disease that develops after acute lung injury and trauma. How released tissue damage signals, or alarmins, orchestrate early inflammatory events is poorly understood. Herein we reveal that IL-33, an alarmin sequestered in the lung epithelium, is required to limit inflammation after injury due to an unappreciated capacity to mediate Foxp3+ Treg control of local cytokines and myeloid populations. Specifically, Il33-/- mice are more susceptible to lung damage-associated morbidity and mortality that is typified by augmented levels of the proinflammatory cytokines and Ly6Chi monocytes in the bronchoalveolar lavage fluid. Local delivery of IL-33 at the time of injury is protective but requires the presence of Treg cells. IL-33 stimulates both mouse and human Tregs to secrete IL-13. Using Foxp3Cre × Il4/Il13fl/fl mice, we show that Treg expression of IL-13 is required to prevent mortality after acute lung injury by controlling local levels of G-CSF, IL-6, and MCP-1 and inhibiting accumulation of Ly6Chi monocytes. Our study identifies a regulatory mechanism involving IL-33 and Treg secretion of IL-13 in response to tissue damage that is instrumental in limiting local inflammatory responses and may shape the myeloid compartment after lung injury.

| S-EPMC6482994 | biostudies-literature

GSTP1 as a novel target in radiation induced lung injury.

Project description:The glutathione S-transferase P1(GSTP1) is an isoenzyme in the glutathione-S transferases (GSTs) enzyme system, which is the most abundant GSTs expressed in adult lungs. Recent research shows that GSTP1 is closely related to the regulation of cell oxidative stress, inhibition of cell apoptosis and promotion of cytotoxic metabolism. Interestingly, there is evidence that GSTP1 single nucleotide polymorphisms (SNP) 105Ile/Val related to the risk of radiation induced lung injury (RILI) development, which strongly suggests that GSTP1 is closely associated with the occurrence and development of RILI. In this review, we discuss our understanding of the role of GSTP1 in RILI and its possible mechanism.

| S-EPMC8268607 | biostudies-literature

IL-20 in Acute Kidney Injury: Role in Pathogenesis and Potential as a Therapeutic Target.

Project description:Acute kidney injury (AKI) causes over 1 million deaths worldwide every year. AKI is now recognized as a major risk factor in the development and progression of chronic kidney disease (CKD). Diabetes is the main cause of CKD as well. Renal fibrosis and inflammation are hallmarks in kidney diseases. Various cytokines contribute to the progression of renal diseases; thus, many drugs that specifically block cytokine function are designed for disease amelioration. Numerous studies showed IL-20 functions as a pro-inflammatory mediator to regulate cytokine expression in several inflammation-mediated diseases. In this review, we will outline the effects of pro-inflammatory cytokines in the pathogenesis of AKI and CKD. We also discuss the role of IL-20 in kidney diseases and provide a potential therapeutic approach of IL-20 blockade for treating renal diseases.

| S-EPMC7037658 | biostudies-literature

Radiation-Induced Lung Injury (RILI).

Project description:Radiation pneumonitis (RP) and radiation fibrosis (RF) are two dose-limiting toxicities of radiotherapy (RT), especially for lung, and esophageal cancer. It occurs in 5-20% of patients and limits the maximum dose that can be delivered, reducing tumor control probability (TCP) and may lead to dyspnea, lung fibrosis, and impaired quality of life. Both physical and biological factors determine the normal tissue complication probability (NTCP) by Radiotherapy. A better understanding of the pathophysiological sequence of radiation-induced lung injury (RILI) and the intrinsic, environmental and treatment-related factors may aid in the prevention, and better management of radiation-induced lung damage. In this review, we summarize our current understanding of the pathological and molecular consequences of lung exposure to ionizing radiation, and pharmaceutical interventions that may be beneficial in the prevention or curtailment of RILI, and therefore enable a more durable therapeutic tumor response.

| S-EPMC6743286 | biostudies-literature

Persistent effects induced by IL-13 in the lung.

Project description:IL-13 overexpression in the lung induces inflammatory and remodeling responses that are prominent features of asthma. Whereas most studies have concentrated on the development of IL-13-induced disease, far fewer studies have focused on the reversibility of IL-13-induced pathologies. This is particularly important because current asthma therapy appears to be poor at reversing lung remodeling. In this manuscript, we used an externally regulatable transgenic system that targets expression of IL-13 to the lung with the aim of characterizing the reversibility process. After 4 wk of doxycycline (dox) exposure, IL-13 expression resulted in mixed inflammatory cell infiltration, mucus cell metaplasia, lung fibrosis, and airspace enlargement (emphysema). After withdrawal of dox, IL-13 protein levels were profoundly reduced by 7 d and below baseline by 14 d. During this time frame, the level of lung eosinophils returned to near normal, whereas macrophages, lymphocytes, and neutrophils remained markedly elevated. IL-13-induced mucus cell metaplasia significantly decreased (91%) 3 wk after withdrawal of dox, showing strong correlation with reduced eosinophil levels. In contrast, IL-13-induced lung fibrosis did not significantly decline 4 wk after dox withdrawal. Importantly, IL-13-induced emphysema persisted, but modestly declined 4 wk after dox. Examination of transcript expression profiles identified a subset of genes that remained increased weeks after transgene expression was no longer detected. Notably, numerous IL-13-induced cytokines and enzymes were reversible (IL-6 and cathepsins), whereas others were sustained (CCL6 and chitinases) after IL-13 withdrawal, respectively. Thus, several hallmark features of IL-13-induced lung pathology persist and are dissociated from eosinophilia after IL-13 overexpression ceases.

| S-EPMC2643287 | biostudies-literature

CPT1A as a potential therapeutic target for lipopolysaccharide-induced acute lung injury in mice.

Project description:Acute lung injury (ALI) remains a high mortality rate with dramatic lung inflammation and alveolar epithelial cell death. Although fatty acid β-oxidation (FAO) impairment has been implicated in the pathogenesis of ALI, whether Carnitine palmitoyltransferase 1A (CPT1A), the rate-limiting enzyme for FAO, plays roles in lipopolysaccharide (LPS)-induced ALI remains unclear. Accordingly, we focused on exploring the effect of CPT1A in the context of ALI and the underlying mechanisms. We found that overexpression of CPT1A (AAV-CPT1A) effectively alleviated lung injury by reduction of lung wet-to-dry ratio, inflammatory cell infiltration, and protein levels in the BALF of ALI mice. Meanwhile, AAV-CPT1A significantly lessened histopathological changes and several cytokines' secretions. In contrast, blocking CPT1A with etomoxir augmented inflammatory responses and lung injury in ALI mice. Furthermore, we found that overexpression of CPT1A with lentivirus reduced the apoptosis rates of alveolar epithelial cells and the expression of apoptosis-related proteins induced by LPS in MLE12 cells, while etomoxir increased the apoptosis of MLE12 cells. Overexpression of CPT1A prevented the drop in bioenergetics, palmitate oxidation, and ATP levels. In conclusion, the results rendered CPT1A worthy of further development into a pharmaceutical drug for the treatment of ALI.

| S-EPMC10796431 | biostudies-literature

Radiation-induced lung injury: current evidence.

Project description:Chemo-radiotherapy and systemic therapies have proven satisfactory outcomes as standard treatments for various thoracic malignancies; however, adverse pulmonary effects, like pneumonitis, can be life-threatening. Pneumonitis is caused by direct cytotoxic effect, oxidative stress, and immune-mediated injury. Radiotherapy Induced Lung Injury (RILI) encompasses two phases: an early phase known as Radiation Pneumonitis (RP), characterized by acute lung tissue inflammation as a result of exposure to radiation; and a late phase called Radiation Fibrosis (RF), a clinical syndrome that results from chronic pulmonary tissue damage. Currently, diagnoses are made by exclusion using clinical assessment and radiological findings. Pulmonary function tests have constituted a significant step in evaluating lung function status during radiotherapy and useful predictive tools to avoid complications or limit toxicity. Systemic corticosteroids are widely used to treat pneumonitis complications, but its use must be standardized, and consider in the prophylaxis setting given the fatal outcome of this adverse event. This review aims to discuss the clinicopathological features of pneumonitis and provide practical clinical recommendations for prevention, diagnosis, and management.

| S-EPMC7788688 | biostudies-literature

Hierarchical control of interleukin 13 (IL-13) signals in lung fibroblasts by STAT6 and SOX11.

Project description:Interleukin (IL)-13 is a signature cytokine of type 2 inflammation important for the pathogenesis of various diseases, including allergic diseases. Signal transducer and activator of transcription (STAT) 6 is a critical transcriptional factor for the IL-13 signals; however, it remains unknown how expression of the IL-13-induced genes is differentiated by the transcriptional machineries. In this study, we identified IL-13-induced transcriptional factors in lung fibroblasts using DNA microarrays in which SOX11 was included. Knockdown of SOX11 down-regulated expression of periostin and CCL26, both of which are known to be downstream molecules of IL-13, whereas enforced expression of SOX11 together with IL-13 stimulation enhanced expression of periostin. Moreover, we found that in DNA microarrays combining IL-13 induction and SOX11 knockdown there exist both SOX11-dependent and -independent molecules in IL-13-inducible molecules. In the former, many inflammation-related and fibrosis-related molecules, including periostin and CCL26, are involved. These results suggest that SOX11 acts as a trans-acting transcriptional factor downstream of STAT6 and that in lung fibroblasts the IL-13 signals are hierarchically controlled by STAT6 and SOX11.

| S-EPMC6153291 | biostudies-literature

IMR90 lung fibroblasts treated with IL-4 or IL-13

Project description:IL-4 and IL-13 are cytokines involved in type 2 immune responses involved in atopic asthma and other diseases. They have a partially overlapping set of cognate receptors whose roles are incompletely understood. Here we explore the effects of these cytokines on lung fibroblasts in order to assess the global similarities and contrasts in the genes whose expression their ligation modulates. IMR-90 lung fibroblast cells were cultured on matrigel or plastic and treated for 24 hours with IL-4 (10 ng/ml), IL-13 (10ng/ml), or TNFa (10 ng/ml) before harvest.

2013-12-31 | E-GEOD-47542 | biostudies-arrayexpress

The IL-4/IL-13 axis in skin fibrosis and scarring: mechanistic concepts and therapeutic targets.

Project description:Skin fibrosis, characterized by excessive fibroblast proliferation and extracellular matrix deposition in the dermis, is the histopathologic hallmark of dermatologic diseases such as systemic sclerosis, hypertrophic scars, and keloids. Effective anti-scarring therapeutics remain an unmet need, underscoring the complex pathophysiologic mechanisms of skin fibrosis. The Th2 cytokines interleukin (IL)-4 and IL-13 have been implicated as key mediators in the pathogenesis of fibroproliferative disorders. The goal of this article is to summarize the current understanding of the role of the IL-4/IL-13 axis in wound healing and skin fibrosis. We conducted a literature search to identify research studies investigating the roles of IL-4 and IL-13 in fibrotic skin diseases. While transforming growth factor-beta has long been regarded as the main driver of fibrotic processes, research into the cellular and molecular biology of wound healing has revealed other pathways that promote scar tissue formation. IL-4 and IL-13 are important mediators of skin fibrosis, supported by evidence from in vitro data, animal models of fibrosis, and clinical studies. Overactive signaling of the IL-4/IL-13 axis contributes to the initiation and perpetuation of fibrotic skin diseases. Further insights into the IL-4/IL-13 axis may reveal potential targets for the development of novel therapies that prevent or treat fibrotic skin diseases.

| S-EPMC7008089 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data