CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats

Lang, Shan; Li, Libing; Wang, Xuning; Sun, Jia; Xue, Xi; Xiao, Yingfeng; Zhang, Mingyue; Ai, Ting; Wang, Jianxin

doi:10.1371/journal.pone.0169100

Cited by 67 publications

(48 citation statements)

References 46 publications

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“…Based on the results obtained in our study, the ALI group presented with lower levels of PaO 2 , while the PaCO 2 , numbers of total cellular score, WBC number, LPI, and the W/D weight ratio had evidently increased when comparing them with the control group. According to previous reports, the recruitment of leukocytes and neutrophil‐mediated lung injury has been reported to play essential roles in the development of ARDS . ARDS, primarily known to be the severe complication of ALI, had been characterized by the accumulation of protein‐rich fluid inside the alveoli, occurring as a result of an increased pulmonary capillary permeability .…”

Section: Discussionmentioning

confidence: 99%

“…According to previous reports, the recruitment of leukocytes and neutrophil-mediated lung injury has been reported to play essential roles in the development of ARDS. 21 ARDS, primarily known to be the severe complication of ALI, had been characterized by the accumulation of protein-rich fluid inside the alveoli, occurring as a result of an increased pulmonary capillary permeability. 22 An increase in the W/D ratio and LPI are two important mechanisms that lead directly to an increase in ARDS inflammation.…”

Section: Discussionmentioning

confidence: 99%

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Protective effects of the suppressed NF‐κB/TLR4 signaling pathway on oxidative stress of lung tissue in rat with acute lung injury

Zhang

Wang

Chen

et al. 2019

The Kaohsiung J of Med Scie

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The pathogenesis of acute lung injury (ALI) is characterized by lung inflammation and lung oxidative stress. The study was conducted in order to investigate the effect toll‐like receptor 4 (TLR4) and nuclear factor‐kappa B (NF‐κB) exhibited on oxidative stress in ALI. After the rats had been assigned into different groups, arterial blood, white blood cell (WBC), lung permeability index (LPI), wet/dry (W/D) ratio, TLR4 and NF‐κB expression and superoxide dismutase (SOD), myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS) were examined. Afterward, the correlation between the levels of TLR4 and NF‐κB was determined. Decreased levels of PaO2, SOD, MPO, and GSH accompanied by increased levels of PaCO2, WBC number, LPI and W/D ratio, MDA and ROS, as well as TLR4 and NF‐κB expressions in the ALI, ALI + NF‐κB inhibitor, and ALI + phosphate buffer saline groups were found. Inhibition of NF‐κB resulted in increased PaO2 and decreased PaCO2 levels, WBC number, and LPI and W/D ratio. Decreased expression of NF‐κB increased SOD, GSH, and MPO, but decreased MDA and ROS. We also found that NF‐κB inhibition resulted in the improvement of ALI in rats. TLR4 and NF‐κB expressions were negatively correlated with levels of SOD, MPO, and GSH, and positively correlated with MDA and ROS levels. In summary, our findings provided evidence that inhibition of the TLR4/NF‐κB signaling pathway decreases oxidative stress, thereby improving ALI. As a result, NF‐κB signaling pathway has shown potential as a therapeutic target in ALI therapy.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Protective effects of the suppressed NF‐κB/TLR4 signaling pathway on oxidative stress of lung tissue in rat with acute lung injury

Zhang

Wang

Chen

et al. 2019

The Kaohsiung J of Med Scie

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“…This trend was flipped in the 72-h infection group, with ST2 KO mice showing significantly higher KC levels than WT mice. IP-10 is a sensitive marker of active rhinovirus infection (27) and has also been shown to contribute to recruitment of various types of leukocytes, such as neutrophils (28). After 16 and 72 h of HRV1B infection, WT and KO mice had increased IP-10 levels in BAL fluid (Fig.…”

Section: St2 In Airway Infection and Inflammationmentioning

confidence: 95%

Interleukin 1 Receptor-Like 1 (IL1RL1) Promotes Airway Bacterial and Viral Infection and Inflammation

et al. 2019

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Interleukin 1 receptor-like 1 (IL1RL1), also known as suppression of tumorigenicity 2 (ST2), is the receptor for interleukin 33 (IL-33) and has been increasingly studied in type 2 inflammation. An increase in airway IL-33/ST2 signaling in asthma has been associated with eosinophilic inflammation, but little is known about the role of ST2 in neutrophilic inflammation. Airway Mycoplasma pneumoniae and human rhinovirus (HRV) infections are linked to neutrophilic inflammation during acute exacerbations of asthma. However, whether ST2 contributes to M. pneumoniae-and HRV-mediated airway inflammation is poorly understood. The current study sought to determine the functions of ST2 during airway M. pneumoniae or HRV infection. In cultured normal human primary airway epithelial cells, ST2 overexpression (OE) increased the production of neutrophilic chemoattractant IL-8 in the absence or presence of M. pneumoniae or HRV1B infection. ST2 OE also enhanced HRV1B-induced IP-10, a chemokine involved in asthma exacerbations. In the M. pneumoniae-infected mouse model, ST2 deficiency, in contrast to sufficiency, significantly reduced the levels of neutrophils following acute (Յ24 h) infection, while in the HRV1B-infected mouse model, ST2 deficiency significantly reduced the levels of proinflammatory cytokines KC, IP-10, and IL-33 in bronchoalveolar lavage (BAL) fluid. Overall, ST2 overexpression in human epithelial cells and ST2 sufficiency in mice increased the M. pneumoniae and HRV loads in cell supernatants and BAL fluid. After pathogen infection, ST2-deficient mice showed a higher level of the host defense protein lactotransferrin in BAL fluid. Our data suggest that ST2 promotes proinflammatory responses (e.g., neutrophils) to airway bacterial and viral infection and that blocking ST2 signaling may broadly attenuate airway infection and inflammation.

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“…Overall, 35/42 (83.3%) participants who received BMS-986184 in the SAD study and 8/12 (66.7%) participants who received BMS-986184 in the MAD study completed the study period. The main reasons for not (4,4) 0.492 18.6 0.313-0.671 ω 2 K a (5,5) 0.181 58.2 0-0.387 ω 2 K in (6,6) 0.117 30.1 0.048-0.186 ω 2 K deg (7,7) 0.031 354.3 0-0.249 ω 2 K int (8,8) 0.034 120.3 0-0.115 ω 2 K SS (9,9) 3.181 58.0 0-6.794 ω 2 F1 (10,10) 0.260 139.6 0-0.97 ω 2 E M AX (11,11) 0.347 170. completing the study were withdrawal of consent (3/54; 5.6%) and adverse events (AEs; 3/54; 5.6%). Baseline characteristics for both the SAD and MAD cohorts are shown in Table 1.…”

Section: Study Populationmentioning

confidence: 99%

“…Interferon (IFN)-γ -induced protein 10 (IP-10/CXC motif chemokine [CXCL]10), a member of the CXC chemokine family, is involved in a diverse range of human diseases, including inflammatory and autoimmune diseases (eg, rheumatoid arthritis, 1 systemic lupus erythematosus, 2 and type 1 diabetes mellitus 3 ) and cancer. [4][5][6] IP-10 is secreted by immune cells (lymphocytes, 7 eosinophils, 8 and monocytes 9 ) and nonimmune cells (hepatocytes, 7 endothelial cells, 9 fibroblasts, 9 stromal cells, 10 and keratinocytes 9 ) in response to inflammatory stimuli, 6,11 and its production is significantly increased in the circulation and diseased tissues of patients with several autoimmune diseases. 12,13 Experimental models of ulcerative colitis (UC) have demonstrated that IP-10 mediates the trafficking of immune cells from the circulation to the in-flamed colon 14 and regulates crypt cell proliferation.…”

mentioning

confidence: 99%

Modeling and Simulation of the Pharmacokinetics and Target Engagement of an Antagonist Monoclonal Antibody to Interferon‐γ–Induced Protein 10, BMS‐986184, in Healthy Participants to Guide Therapeutic Dosing

Cai

Leil

Gibiansky³

et al. 2020

Clinical Pharm in Drug Dev

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BMS-986184 is a human, second-generation, anti-interferon-γ-induced protein 10 (IP-10) monoclonal antibody. In this study the pharmacokinetics and target engagement (TE) of BMS-986184 in healthy participants were characterized using population-based target-mediated drug disposition (TMDD) modeling and data from a first-in-human study (NCT02864264). The results of the first-in-human study and the model generated were used to conduct stochastic simulations of a virtual population of healthy participants to predict pharmacokinetic exposures and TE responses for different dosage regimens. A 2-compartment, 2-target, TMDD structural model, assuming quasi-steady-state and stimulated production on treatment, was developed by simultaneous fitting of the total drug, serum-free IP-10, and serum total IP-10 concentration data, with the second unobservable target contribution to drug elimination described by the Michaelis-Menten elimination term. Model evaluation confirmed agreement between model predictions and observed data. Simulation of a virtual population of healthy individuals demonstrated that steady state was reached at the eighth dosing interval, and that around 150 mg subcutaneously every other week could be a suitable target dosage regimen for future clinical trials.Integrated modeling strategies such as this can be used to help guide rational clinical trial development of drugs with TMDD, leading to improved dose selection and greater patient benefits.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.Additional supplemental information can be found by clicking the Supplements link in the PDF toolbar or the Supplemental Information section at the end of webbased version of this article.

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CXCL10/IP-10 Neutralization Can Ameliorate Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome in Rats

Cited by 67 publications

References 46 publications

Protective effects of the suppressed NF‐κB/TLR4 signaling pathway on oxidative stress of lung tissue in rat with acute lung injury

Protective effects of the suppressed NF‐κB/TLR4 signaling pathway on oxidative stress of lung tissue in rat with acute lung injury

Interleukin 1 Receptor-Like 1 (IL1RL1) Promotes Airway Bacterial and Viral Infection and Inflammation

Modeling and Simulation of the Pharmacokinetics and Target Engagement of an Antagonist Monoclonal Antibody to Interferon‐γ–Induced Protein 10, BMS‐986184, in Healthy Participants to Guide Therapeutic Dosing

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