Mucin1 relieves acute lung injury by inhibiting inflammation and oxidative stress

Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a kind of diffuse inflammatory injury caused by various factors, characterized by respiratory distress and progressive hypoxemia. It is a common clinical critical illness. The aim of this study was to investigate the effect and mechanism of the Mucin1 (MUC1) gene and its recombinant protein on lipopolysaccharide (LPS)-induced ALI/ARDS. We cultured human alveolar epithelial cell line (BEAS-2B) and used MUC1 overexpression lentivirus to detect the effect of MUC1 gene on BEAS-2B cells. In addition, we used LPS to induce ALI/ARDS in C57/BL6 mice and use hematoxylin and eosin (H&E) staining to verify the effect of their modeling. Recombinant MUC1 protein was injected subcutaneously into mice. We examined the effect of MUC1 on ALI/ARDS in mice by detecting the expression of inflammatory factors and oxidative stress molecules in mouse lung tissue, bronchoalveolar lavage fluid (BALF) and serum. Overexpression of MUC1 effectively ameliorated LPS-induced damage to BEAS-2B cells. Results of H&E staining indicate that LPS successfully induced ALI/ARDS in mice and MUC1 attenuated lung injury. MUC1 also reduced the expression of inflammatory factors (IL-1β, TNF-α, IL-6 and IL-8) and oxidative stress levels in mice. In addition, LPS results in an increase in the activity of the TLR4/NF-κB signaling pathway in mice, whereas MUC1 decreased the expression of the TLR4/NF-κB signaling pathway. MUC1 inhibited the activity of TLR4/NF-κB signaling pathway and reduced the level of inflammation and oxidative stress in lung tissue of ALI mice.Key words: Mucin1, acute lung injury, inflammation, oxidative stress, TLR4/NF-κB     

Immunosuppressive effect of mesenchymal stem cells on lung and gut CD8+ T cells in lipopolysaccharide‐induced acute lung injury in mice

ObjectivesAcute lung injury (ALI) not only affects pulmonary function but also leads to intestinal dysfunction, which in turn contributes to ALI. Mesenchymal stem cell (MSC) transplantation can be a potential strategy in the treatment of ALI. However, the mechanisms of synergistic regulatory effects by MSCs on the lung and intestine in ALI need more in‐depth study.Materials and methodsWe evaluated the therapeutic effects of MSCs on the murine model of lipopolysaccharide (LPS)‐induced ALI through survival rate, histopathology and bronchoalveolar lavage fluid. Metagenomic sequencing was performed to assess the gut microbiota. The levels of pulmonary and intestinal inflammation and immune response were assessed by analysing cytokine expression and flow cytometry.ResultsMesenchymal stem cells significantly improved the survival rate of mice with ALI, alleviated histopathological lung damage, improved intestinal barrier integrity, and reduced the levels of inflammatory cytokines in the lung and gut. Furthermore, MSCs inhibited the inflammatory response by decreasing the infiltration of CD8⁺ T cells in both small‐intestinal lymphocytes and Peyer''s patches. The gut bacterial community diversity was significantly altered by MSC transplantation. Furthermore, depletion of intestinal bacterial communities with antibiotics resulted in more severe lung and gut damages and mortality, while MSCs significantly alleviated lung injury due to their immunosuppressive effect.ConclusionsThe present research indicates that MSCs attenuate lung and gut injury partly via regulation of the immune response in the lungs and intestines and gut microbiota, providing new insights into the mechanisms underlying the therapeutic effects of MSC treatment for LPS‐induced ALI.     

FGF21 alleviates acute liver injury by inducing the SIRT1‐autophagy signalling pathway

Liver injury can lead to different hepatic diseases, which are the mainly causes of high global mortality and morbidity. Autophagy and Sirtuin type 1 (SIRT1) have been shown protective effects in response to liver injury. Previous studies have showed that Fibroblast growth factor 21 (FGF21) could alleviate acute liver injury (ALI), but the mechanism remains unclear. Here, we verified the relationship among FGF21, autophagy and SIRT1 in carbon tetrachloride (CCl₄)‐induced ALI. We established CCl₄‐induced ALI models in C57BL/6 mice and the L02 cell line. The results showed that FGF21 was robustly induced in response to stress during the development of ALI. After exogenous FGF21 treatment in ALI models, liver damage in ALI mice was significantly reduced, as well as serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Consistently, FGF21 also greatly reduced the levels of ALT, AST, pro‐inflammatory cytokines interleukin 6 (IL6) and tumour necrosis factor‐alpha (TNFα) in ALI cell lines. Mechanistically, exogenous FGF21 treatment efficiently upregulated the expression of autophagy marker microtubule‐associated protein light chain‐3 beta (LC3 II) and autophagy key molecule coiled‐coil myosin‐like BCL2‐interacting protein (Beclin1), which was accompanied by alleviating hepatotoxicity in CCl₄‐treated wild‐type mice. Then, we examined how FGF21 induced autophagy expression and found that SIRT1 was also upregulated by FGF21 treatment. To further verify our results, we constructed an anti‐SIRT1 lentit‐RNAi to inhibit SIRT1 expression in mice and L02 cells, which reversed the protective effect of FGF21 on ALI. In summary, these results indicate that FGF21 alleviates ALI by enhancing SIRT1‐mediated autophagy.     

Glycyrrhizic Acid Prevents Sepsis-Induced Acute Lung Injury and Mortality in Rats

Glycyrrhizic acid (GA), an active ingredient in licorice, has multiple pharmacological activities. However, the effects of GA on sepsis-induced acute lung injury (ALI) have not been determined. Tthe aim of this study was to investigate the molecular mechanism involved in the effects of GA against sepsis-induced ALI in rats. We found that GA alleviated sepsis-induced ALI through improvements in various pathological changes, as well as decreases in the lung wet/dry weight ratio and total protein content in bronchoalveolar lavage fluid, and a significant increase in the survival rate of treated rats. Additionally, GA markedly inhibited sepsis-induced pulmonary inflammatory responses. Moreover, we found that treatment with GA inhibited oxidative stress damage and apoptosis in lung tissue induced by ALI. Finally, GA treatment significantly inhibited NF-κ B, JNK and P38 MAPK activation. Our data indicate that GA has a protective effect against sepsis-induced ALI by inhibiting the inflammatory response, damage from oxidative stress, and apoptosis via inactivation of NF-κB and MAPK signaling pathways, providing a molecular basis for a new medical treatment for sepsis-induced ALI.     

Caveolin‐1 negatively regulates inflammation and fibrosis in silicosis

Inhalation of crystalline silica causes silicosis, the most common and serious occupational disease, which is characterized by progressive lung inflammation and fibrosis. Recent studies revealed the anti‐inflammatory and anti‐fibrosis role of Caveolin‐1 (Cav‐1) in lung, but this role in silicosis has not been investigated. Thus, this study evaluated Cav‐1 regulatory effects in silicosis. It was found that Cav‐1 levels were significantly reduced in the lung from silicosis patients and silicotic mice. The silicosis models were established in C57BL/6 (wild‐type) and Cav‐1 deficiency (Cav‐1 ^−/−) mice, and Cav‐1 ^−/− mice displayed wider alveolar septa, increased collagen deposition and more silicotic nodules. The mice peritoneal‐derived macrophages were used to explore the role of Cav‐1 in silica‐induced inflammation, which plays a central role in mechanism of silicosis. Cav‐1 inhibited silica‐induced infiltration of inflammatory cells and secretion of inflammatory factors in vitro and in vivo, partly by downregulating NF‐κB pathway. Additionally, silica uptake and expression of 4‐hydroxynonenal in silicotic mice were observed, and it was found that Cav‐1 absence triggered excessive silica deposition, causing a stronger oxidative stress response. These findings demonstrate the protective effects of Cav‐1 in silica‐induced lung injury, suggesting its potential therapeutic value in silicosis.     

Ursodeoxycholic acid protects against lung injury induced by fat embolism syndrome

Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is a life‐threatening disease with a high mortality rate, which was a common complication of fat embolism syndrome (FES). Ursodeoxycholic acid (UDCA) has been reported to exert potent anti‐inflammatory effects under various conditions. In vivo, perinephric fat was injected via tail vein to establish a rat FES model, the anti‐inflammatory effects of UDCA on FES‐induced lung injury were investigated through histological examination, ELISA, qRT‐PCR, Western blot and immunofluorescence. In vitro, human lung microvascular endothelial cells (HPMECs) were employed to understand the protective effects of UDCA. The extent of ALI/ARDS was evaluated and validated by reduced PaO₂/FiO₂ ratios, increased lung wet/dry (W/D) ratios and impaired alveolar‐capillary barrier, up‐regulation of ALI‐related proteins in lung tissues (including myeloperoxidase [MPO], vascular cell adhesion molecule 1 [VCAM‐1], intercellular cell adhesion molecule‐1 [ICAM‐1]), elevated protein concentration and increased proinflammatory cytokines levels (TNF‐α and IL‐1β) in bronchoalveolar lavage fluid (BALF). Pre‐treatment with UDCA remarkably alleviated these pathologic and biochemical changes of FES‐induced ALI/ARDS; our data demonstrated that pre‐treatment with UDCA attenuated the pathologic and biochemical changes of FES‐induced ARDS, which provided a possible preventive therapy for lung injury caused by FES.     

Protectin DX promotes epithelial injury repair and inhibits fibroproliferation partly via ALX/PI3K signalling pathway

Acute respiratory distress syndrome/acute lung injury (ARDS/ALI) is histologically characterized by extensive alveolar barrier disruption and excessive fibroproliferation responses. Protectin DX (PDX) displays anti‐inflammatory and potent inflammation pro‐resolving actions. We sought to investigate whether PDX attenuates LPS (lipopolysaccharide)‐induced lung injury via modulating epithelial cell injury repair, apoptosis and fibroblasts activation. In vivo, PDX was administered intraperitoneally (IP) with 200 ng/per mouse after intratracheal injection of LPS, which remarkedly stimulated proliferation of type II alveolar epithelial cells (AT II cells), reduced the apoptosis of AT II cells, which attenuated lung injury induced by LPS. Moreover, primary type II alveolar cells were isolated and cultured to assess the effects of PDX on wound repair, apoptosis, proliferation and transdifferentiation in vitro. We also investigated the effects of PDX on primary rat lung fibroblast proliferation and myofibroblast differentiation. Our result suggests PDX promotes primary AT II cells wound closure by inducing the proliferation of AT II cells and reducing the apoptosis of AT II cells induced by LPS, and promotes AT II cells transdifferentiation. Furthermore, PDX inhibits transforming growth factor‐β₁ (TGF‐β₁) induced fibroproliferation, fibroblast collagen production and myofibroblast transformation. Furthermore, the effects of PDX on epithelial wound healing and proliferation, fibroblast proliferation and activation partly via the ALX/ PI3K signalling pathway. These data present identify a new mechanism of PDX which targets the airway epithelial cell and fibroproliferation are potential for treatment of ARDS/ALI.     

Induction of acute respiratory distress syndrome in rats by lipopolysaccharide and its effect on oxidative stress and antioxidant status in lung

Acute lung injury (ALI) or its severe form, acute respiratory distress syndrome (ARDS) is an important cause of mortality in the human population. Despite significant advances made, the mortality associated with ALI remains unchanged. The objective of the present study was to evaluate the role of oxidative stress, alveolar antioxidant status and multiple organ injury in ARDS induced by lipopolysaccharide (LPS) in rats. Rats were divided into 4 groups, group I control rats were given saline intraperitoneally, whereas groups II, III and IV (LPS-treated) rats received an intraperitoneal injection of LPS (10 mg/kg body weight) and sacrificed after various time intervals. In LPS-treated rats, we observed increased levels of oxidative products, decreased levels of antioxidants in lung tissues and increased levels of serum marker enzymes, suggesting multiple organ injury. Bronchoalveolar lavage fluid (BALF) neutrophil content and protein concentration in LPS-treated rats were significantly elevated in a time-dependent manner. Histological studies revealed neutrophil influx and diffused alveolar damage in LPS-administered rats. These results clearly suggested that increased oxidant levels led to oxidative stress, antioxidant deficiency attenuating lung inflammation and tissue damage. LPS administration resulted in multiple organ failure, leading to increased mortality.     

The role of Cold‐Inducible RNA‐binding protein in respiratory diseases

Cold‐inducible RNA‐binding protein (CIRP) is a stress‐response protein that is expressed in various types of cells and acts as an RNA chaperone, modifying the stability of its targeted mRNA. Intracellular CIRP could also be released into extracellular space and once released, extracellular CIRP (eCIRP) acts as a damage‐associated molecular pattern (DAMP) to induce and amplify inflammation. Recent studies have found that eCIRP could promote acute lung injury (ALI) via activation of macrophages, neutrophils, pneumocytes and lung vascular endothelial cells in context of sepsis, haemorrhagic shock, intestinal ischemia/reperfusion injury and severe acute pancreatitis. In addition, CIRP is also highly expressed in the bronchial epithelial cells and its expression is upregulated in the bronchial epithelial cells of patients with chronic obstructive pulmonary diseases (COPD) and rat models with chronic bronchitis. CIRP is a key contributing factor in the cold‐induced exacerbation of COPD by promoting the expression of inflammatory genes and hypersecretion of airway mucus in the bronchial epithelial cells. Besides, CIRP is also involved in regulating pulmonary fibrosis, as eCIRP could directly activate and induce an inflammatory phenotype in pulmonary fibroblast. This review summarizes the findings of CIRP investigation in respiratory diseases and the underlying molecular mechanisms.     

MG53 attenuates nitrogen mustard‐induced acute lung injury

Nitrogen mustard (NM) is an alkylating vesicant that causes severe pulmonary injury. Currently, there are no effective means to counteract vesicant‐induced lung injury. MG53 is a vital component of cell membrane repair and lung protection. Here, we show that mice with ablation of MG53 are more susceptible to NM‐induced lung injury than the wild‐type mice. Treatment of wild‐type mice with exogenous recombinant human MG53 (rhMG53) protein ameliorates NM‐induced lung injury by restoring arterial blood oxygen level, by improving dynamic lung compliance and by reducing airway resistance. Exposure of lung epithelial and endothelial cells to NM leads to intracellular oxidative stress that compromises the intrinsic cell membrane repair function of MG53. Exogenous rhMG53 protein applied to the culture medium protects lung epithelial and endothelial cells from NM‐induced membrane injury and oxidative stress, and enhances survival of the cells. Additionally, we show that loss of MG53 leads to increased vulnerability of macrophages to vesicant‐induced cell death. Overall, these findings support the therapeutic potential of rhMG53 to counteract vesicant‐induced lung injury.     

The dynamic changes in autophagy activity and its role in lung injury after deep hypothermic circulatory arrest

Deep hypothermic circulatory arrest (DHCA) can cause acute lung injury (ALI), and its pathogenesis mimics ischaemia/reperfusion (I/R) injury. Autophagy is also involved in lung I/R injury. The present study aimed to elucidate whether DHCA induces natural autophagy activation and its role in DHCA‐mediated lung injury. Here, rats were randomly assigned to the Sham or DHCA group. The sham group (n = 5) only received anaesthesia and air intubation. DHCA group rats underwent cardiopulmonary bypass (CPB) followed by the DHCA procedure. The rats were then sacrificed at 3, 6 and 24 h after the DHCA procedure (n = 5) to measure lung injury and autophagy activity. Chloroquine (CQ) was delivered to evaluate autophagic flux. DHCA caused lung injury, which was prominent 3–6 h after DHCA, as confirmed by histological examination and inflammatory cytokine quantification. Lung injury subsided at 24 h. Autophagy was suppressed 3 h but was exaggerated at 6 h. At both time points, autophagic flux appeared uninterrupted. To further assess the role of autophagy in DHCA‐mediated lung injury, the autophagy inducer rapamycin and its inhibitor 3‐methyladenine (3‐MA) were applied, and lung injury was reassessed. When rapamycin was administered at an early time point, lung injury worsened, whereas administration of 3‐MA at a late time point ameliorated lung injury, indicating that autophagy contributed to lung injury after DHCA. Our study presents a time course of lung injury following DHCA. Autophagy showed adaptive yet protective suppression 3 h after DHCA, as induction of autophagy caused worsening of lung tissue. In contrast, autophagy was exaggerated 6 h after DHCA, and autophagy inhibition attenuated DHCA‐mediated lung injury.     

CTRP3 protects against uric acid-induced endothelial injury by inhibiting inflammation and oxidase stress in rats

Hyperuricemia, which contributes to vascular endothelial damage, plays a key role in multiple cardiovascular diseases. This study was designed to investigate whether C1q/tumor necrosis factor (TNF)-related protein 3 (CTRP3) has a protective effect on endothelial damage induced by uric acid and its underlying mechanisms. Animal models of hyperuricemia were established in Sprague-Dawley (SD) rats through the consumption of 10% fructose water for 12 weeks. Then, the rats were given a single injection of Ad-CTRP3 or Ad-GFP. The animal experiments were ended two weeks later. In vitro, human umbilical vein endothelial cells (HUVECs) were first infected with Ad-CTRP3 or Ad-GFP. Then, the cells were stimulated with 10 mg/dL uric acid for 48 h after pretreatment with or without a Toll-like receptor 4 (TLR4)-specific inhibitor. Hyperuricemic rats showed disorganized intimal structures, increased endothelial apoptosis rates, increased inflammatory responses and oxidative stress, which were accompanied by reduced CTRP3 and elevated TLR4 protein levels in the thoracic aorta. In contrast, CTRP3 overexpression decreased TLR4 protein levels and ameliorated inflammatory responses and oxidative stress, thereby improving the morphology and apoptosis of the aortic endothelium in rats with hyperuricemia. Similarly, CTRP3 overexpression decreased TLR4-mediated inflammation, reduced oxidative stress, and rescued endothelial damage induced by uric acid in HUVECs. In conclusion, CTRP3 ameliorates uric acid-induced inflammation and oxidative stress, which in turn protects against endothelial injury, possibly by inhibiting TLR4-mediated inflammation and downregulating oxidative stress.     

Intratracheal transplantation of human umbilical cord blood-derived mesenchymal stem cells attenuates Escherichia coli-induced acute lung injury in mice

Background

Human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) attenuate hyperoxic neonatal lung injury primarily through anti-inflammatory effects. We hypothesized that intratracheal transplantation of human UCB-derived MSCs could attenuate Escherichia coli (E. coli)-induced acute lung injury (ALI) in mice by suppressing the inflammatory response.

Methods

Eight-week-old male ICR mice were randomized to control or ALI groups. ALI was induced by intratracheal E. coli instillation. Three-hours after E. coli instillation, MSCs, fibroblasts or phosphate-buffered saline were intratracheally administered randomly and survival was analyzed for 7 days post-injury. Lung histology including injury scores, myeloperoxidase (MPO) activity, and protein levels of interleukin (IL)-1α, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein (MIP)-2 as well as the wet-dry lung ratio and bacterial counts from blood and bronchoalveolar lavage (BAL) were evaluated at 1, 3, and 7 days post-injury. Levels of inflammatory cytokines in the lung were also profiled using protein macroarrays at day 3 post-injury which showed peak inflammation.

Results

MSC transplantation increased survival and attenuated lung injuries in ALI mice, as evidenced by decreased injury scores on day 3 post-injury and reduced lung inflammation including increased MPO activity and protein levels of IL-1α, IL-1β, IL-6, TNF-α, and MIP-2 on day 3 and 7 post-injury. Inflammatory cytokine profiles in the lungs at day 3 post-injury were attenuated by MSC transplantation. MSCs also reduced the elevated lung water content at day 3 post-injury and bacterial counts in blood and BAL on day 7 post-injury.

Conclusions

Intratracheal transplantation of UCB-derived MSCs attenuates E. coli-induced ALI primarily by down-modulating the inflammatory process and enhancing bacterial clearance.     

Inhibition of glycolysis alleviates lipopolysaccharide-induced acute lung injury in a mouse model

Gluconic metabolic reprogramming, immune response, and inflammation are intimately linked. Glycolysis involves in the pathologic progress in acute and chronic inflammatory diseases. However, the involvement of glycolysis in the acute lung injury (ALI) is still unclear. This study investigated the role of glycolysis in an animal model of ALI. First, we found that lactate content in serum was remarkably increased in ALI patients and a murine model induced by intratracheal administration of lipopolysaccharide (LPS). The key proteins involving in glycolysis were robustly elevated, including HK2, PKM2, and HIF-1α. Intriguingly, inhibition of glycolysis by 2-deoxyglucose (2-DG) pronouncedly attenuated the lung tissue pathological injury, accumulation of neutrophil, oxidative stress, expression of proinflammatory factors in the lung of ALI mice induced by LPS. The 2-DG treatment also strongly suppressed the activation of the NOD-like receptor (NLR) family and pyrin domain-containing protein 3 (NLRP3) inflammasome. Furthermore, we investigated the role of glycolysis in the inflammatory response of primary murine macrophages activated by LPS in vitro. We found that the 2-DG treatment remarkably reduced the expression of proinflammatory factors induced by LPS, including tumor necrosis factor-α messenger RNA (mRNA), pro-interleukin (IL)-1β mRNA, pro-IL-18 mRNA, NLRP3 mRNA, caspase-1 mRNA, and IL-1β protein. Altogether, these data provide a novel link between gluconic metabolism reprogramming and uncontrolled inflammatory response in ALI. This study suggests glycolytic inhibition as an effective anti-inflammatory strategy in treating ALI.     

Antrodia camphorata polysaccharide improves inflammatory response in liver injury via the ROS/TLR4/NF‐κB signal

Antrodia Camphorata Polysaccharide (ACP) refers to a kind of polysaccharide extracted from the natural porous fungus Antrodia camphorata. This study investigated the mechanism of action of ACP in protecting the liver. The results showed that ACP suppressed the LPS‐induced KC cell activation, reduced the expression of inflammatory factors, increased the SOD level and suppressed ROS expression. In addition, N‐acetylcysteine (NAC) was adopted for pre‐treatment to suppress ROS. The results indicated that NAC synergistically exerted its effect with ACP, suggesting that ACP played its role through suppressing ROS. Further detection revealed that ACP activated the Nrf2 signal. It was discovered in the mouse model that, ACP effectively improved liver injury in mice, decreased ALT and AST levels, and suppressed the expression of inflammatory factors. This study suggests that ACP can exert its effect against oxidative stress via the Nrf2‐ARE signalling, which further improves the production of ROS and the activation of TLR4‐NF‐κB signalling, and protects the liver against liver injury.     

E3 ubiquitin ligase NEDD4L negatively regulates keratinocyte hyperplasia by promoting GP130 degradation

Psoriasis is mainly characterized by abnormal hyperplasia of keratinocytes and immune cells infiltrating into the dermis and epidermis. Neural precursor cell expressed developmentally downregulated 4‐like (NEDD4L) is a highly conserved HECT type E3 ligase that plays an important role in regulating physiological and pathological processes. Here, we identify NEDD4L as a negative regulator of psoriasis. Nedd4l significantly inhibits imiquimod (IMQ)‐induced skin hyperplasia, and this effect is attributed to the inhibitory effect of NEDD4L on IL‐6/GP130 signaling in keratinocytes. Mechanistically, NEDD4L directly interacts with GP130 and mediates its Lys‐27‐linked ubiquitination and proteasomal degradation. Moreover, the expression of NEDD4L is downregulated in the epidermis from IMQ‐treated mice and psoriasis patients and negatively correlates with the protein levels of GP130 and p‐STAT3 in clinical samples. Collectively, we uncover an inhibitory role of NEDD4L in the pathogenesis of psoriasis and suggest a new therapeutic strategy for the treatment of psoriasis.     

Roles of mesenchymal stem cells and exosomes in interstitial cystitis/bladder pain syndrome

Interstitial cystitis/bladder pain syndrome (IC/BPS) is characterized by several symptoms of higher sensitivity of the lower urinary tract, such as bladder pain/discomfort, urgency, urinary frequency, pelvic pain and nocturia. Although the pathophysiology of IC/BPS is not fully understood, the hypothesis suggests that mast cell activation, glycosaminoglycan (GAG) layer defects, urothelium permeability disruption, inflammation, autoimmune disorder and infection are potential mechanisms. Mesenchymal stem cells (MSCs) have been proven to protect against tissue injury in IC/BPS by migrating into bladders, differentiating into key bladder cells, inhibiting mast cell accumulation and cellular apoptosis, inhibiting inflammation and oxidative stress, alleviating collagen fibre accumulation and enhancing tissue regeneration in bladder tissues. In addition, MSCs can protect against tissue injury in IC/BPS by secreting various soluble factors, including exosomes and other soluble factors, with antiapoptotic, anti‐inflammatory, angiogenic and immunomodulatory properties in a cell‐to‐cell independent manner. In this review, we comprehensively summarized the current potential pathophysiological mechanisms and standard treatments of IC/BPS, and we discussed the potential mechanisms and therapeutic effects of MSCs and MSC‐derived exosomes in alleviating tissue injury in IC/BPS models.     

PARP-1 Inhibitor,DPQ, Attenuates LPS-Induced Acute Lung Injury through Inhibiting NF-κB-Mediated Inflammatory Response

Acute lung injury (ALI) is characterized by overwhelming lung inflammation and anti-inflammation treatment is proposed to be a therapeutic strategy for ALI. Poly (ADP-ribose) polymerase-1 has been demonstrated to be involved in tissue inflammation and one of its inhibitors, 3, 4-Dihydro-5[4-(1-piperindinyl)butoxy]-1(2H)-isoquinoline (DPQ), exerts anti-inflammatory effect. However, it is still unclear whether the DPQ possesses the protective effect on ALI and what mechanisms are involved. In this study, we tested the effect of DPQ on the lung inflammation induced by lipopolysaccharide (LPS) challenge in mice. We found that 6 h-LPS challenge induced significant lung inflammation and vascular leakage in mice. Treatment with DPQ at the dose of 10 μg/kg markedly reduced the neutrophil infiltration, myeloperoxidase activity and up-regulation of pro-inflammatory mediators and cytokines. LPS-elevated vascular permeability was decreased by DPQ treatment, accompanied by the inhibition of apoptotic cell death in mice lungs. In addition, we isolated mice peritoneal macrophages and showed pretreatment with DPQ at 10 μM inhibited the production of cytokines in the macrophages following LPS stimulation. DPQ treatment also inhibited the phosphorylation and degradation of IκB-α, subsequently blocked the activation of nuclear factor (NF)-κB induced by LPS in vivo and in vitro. Taken together, our results show that DPQ treatment inhibits NF-κB signaling in macrophages and protects mice against ALI induced by LPS, suggesting inhibition of Poly (ADP-ribose) polymerase-1 may be a potential and effective approach to resolve inflammation for the treatment of ALI.