Anti-inflammatory mechanism of ulinastatin: Inhibiting the hyperpermeability of vascular endothelial cells induced by TNF-α via the RhoA/ROCK signal pathway

Fu, Wei; Liu, Si Yi; Lu, Luo; Gu, Ni; Zeng, Yan; Chen, Xiao Ying; Xu, Shan; Zhang, Dan

doi:10.1016/j.intimp.2017.03.007

Cited by 36 publications

(30 citation statements)

References 31 publications

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“…From the viewpoint of relatively long duration before withdrawal and various side effects, corticosteroid use is best avoided, if possible. In addition, although the in vitro anti-inflammatory effect of ulinastatin has been shown (27), its effect on liver inflammation in the clinical setting has not yet been reported.…”

Section: Discussionmentioning

confidence: 98%

Adjuvant recombinant thrombomodulin therapy for hepatopathy induced by vincristine, actinomycin D, and cyclophosphamide in pediatric rhabdomyosarcoma: A case report

et al. 2019

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Hepatopathy induced by vincristine, actinomycin D and cyclophosphamide (VAC) is a potentially lethal complication of VAC chemotherapy for pediatric malignancy, which is managed by conventional anticoagulation and liver-supporting treatment alone. We report a case of VAC-induced hepatopathy with coagulopathy and severe inflammation. A 15-year-old male with rhabdomyosarcoma receiving adjuvant chemotherapy presented with refractory thrombocytopenia, followed by abdominal tenderness and non-neutropenic fever. Hepatic dysfunction and coagulopathy subsequently emerged with persistent fever. This condition indicated disseminated intravascular coagulation. A diagnosis of 'very severe' sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD) was established in accordance with the European Society for Blood and Marrow Transplantation diagnostic criteria for hepatic SOS/VOD in children. Early administration of recombinant thrombomodulin (rTM) (380 U/kg/day) and prednisolone (1.8 mg/kg/day) successfully controlled the condition. Serum concentrations of pro-inflammatory cytokines increased with hepatopathy development but immediately decreased after drug initiation. rTM administration may be promising for the control of inflammatory VAC-induced hepatopathy.

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Section: Discussionmentioning

confidence: 98%

Adjuvant recombinant thrombomodulin therapy for hepatopathy induced by vincristine, actinomycin D, and cyclophosphamide in pediatric rhabdomyosarcoma: A case report

et al. 2019

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“…There is strong evidence indicating protective effects of UTI against sepsis-induced multiorgan injuries, such as acute lung injury (Fang et al, 2018). It has been demonstrated that UTI relieves TNF-α induced hyperpermeability of vascular endothelial cells (We et al, 2017). In addition, UTI can effectively inhibit inflammation and reduce protein expression of AQP-4 (Cui and Zhu, 2015), which helps to attenuate capillary permeability and, as a result, alleviates lung and neural injuries.…”

Section: Discussionmentioning

confidence: 99%

“…It is capable of suppressing various serine proteases such as trypsin, plasmin, neutrophil elastase and chymotrypsin (Nishiyama et al, 1996;Nakatani et al, 2001), and can also effectively stabilize lysosomal and cellular membranes (Nakahama et al, 1999). UTI has confirmed powerful efficacy in inhibiting the release of inflammatory factors, removing oxygen free radicals, improving microcirculation and tissue perfusion, and alleviating endothelial injuries (Takada et al, 2003;Tanaka et al, 2010;We et al, 2017;Fang et al, 2018). Clinically, UTI has been applied effectively in treating acute pancreatitis, acute circulatory failure, and ischemia-reperfusion injury with few adverse events (Yoo et al, 2008;Li et al, 2017).…”

Section: Introductionmentioning

confidence: 99%

Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness

Meng¹,

Qing²,

et al. 2020

Front. Physiol.

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Inflammatory reaction is the crux in various clinical critical diseases including decompression sickness (DCS). Ulinastatin (UTI), a potent anti-inflammatory agent, has been used clinically, including as a substitution for steroids. This study aimed to explore the potential effects of UTI upon DCS in a rabbit model. Eighty-eight rabbits were subjected to simulated diving to 6 atmospheres absolute (ATA) for 60 min with 2.5minute decompression. Three doses of UTI (15/7.5/3.75 × 10 5 U/kg) or saline were intravenously administered immediately following decompression. Circulating bubbles were monitored for 3 h following decompression and DCS signs were evaluated for 24 h. Blood was sampled 8 times during 72 h after decompression for inflammatory, endothelial, oxidative and routine blood indices. Lung tissues were also sampled for evaluating endothelial function. Another six rabbits were used as Normal controls. In the high dose UTI group the mortality, general morbidity and incidence of severe DCS was decreased from 31.25 to 9.38% (P = 0.030), 84.38 to 62.50% (P = 0.048) and 46.88 to 21.88% (P = 0.035), respectively. The high dose of UTI significantly postponed the occurrence of DCS (P = 0.030) and prolonged survival time (P = 0.009) compared with the Saline group, and significantly ameliorated inflammation responses, endothelial injuries and oxidative damage. The results strongly suggest the benefit of UTI on DCS, especially for severe cases. Large doses are needed to achieve significant effects. UTI may be a potential ideal pharmacological candidate for the treatment of severe DCS.

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“…The RhoA/Rho pathway is responsible for determining the balance between the actin polymerization and depolymerization processes, which triggers a caspase cascade. Its role in the biological processes has mainly been described concerning cell migration, proliferation, and apoptosis [38,39]. In their studies, Li et al showed the role of RhoA in maintaining the state of homeostasis between the number of Treg lymphocytes and Th17-type lymphocytes [40].…”

Section: Discussionmentioning

confidence: 99%

mRNA level of ROCK1, RHOA, and LIMK2 as genes associated with apoptosis in evaluation of effectiveness of adalimumab treatment

Krawczyk

Strzałka‐Mrozik

Grabarek³

et al. 2020

Pharmacol. Rep

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Background Psoriasis is a multifactorial autoimmune disease, which underlies the abnormalities of the apoptotic process. In cases of psoriasis and psoriatic arthritis, biological treatment is used. This study aimed to determine any changes in the expression of the genes associated with apoptosis in patients with psoriatic arthritis treated with adalimumab and to assess any phenotypic modifications based on changes in dermatological indexes. Methods The study included 20 patients with psoriatic arthritis treated biologically and 20 healthy volunteers. The research material consisted of peripheral blood mononuclear cells (PBMCs) from which the total RNA was isolated. Changes in the gene expression were determined using oligonucleotide microarrays and RT-qPCR. The clinical condition was assessed based on selected indicators: PASI, BSA [%], DAS28, and DLQI, which were determined every 3 months. Results There were changes in the expression of genes associated with apoptosis. Significant differences were found for ROCK1, RhoA, and LIMK2 expression profiles in PBMCs. At the initial stage of treatment, a decrease in the PASI and BSA rates was observed. At the later stages, the values of these indicators increased once again. There were correlations between the changes in these genes' expression and the dermatological markers. Conclusion Adalimumab influences the expression of genes related to apoptosis and the values of dermatological indicators of patients. Changes in the expression level of genes associated with apoptosis suggest that ROCK1, RhoA, and LIMK2 may be genes that can potentially be indicators of treatment effectiveness and lack of response to biological treatment.

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Anti-inflammatory mechanism of ulinastatin: Inhibiting the hyperpermeability of vascular endothelial cells induced by TNF-α via the RhoA/ROCK signal pathway

Cited by 36 publications

References 31 publications

Adjuvant recombinant thrombomodulin therapy for hepatopathy induced by vincristine, actinomycin D, and cyclophosphamide in pediatric rhabdomyosarcoma: A case report

Adjuvant recombinant thrombomodulin therapy for hepatopathy induced by vincristine, actinomycin D, and cyclophosphamide in pediatric rhabdomyosarcoma: A case report

Ulinastatin: A Potential Alternative to Glucocorticoid in the Treatment of Severe Decompression Sickness

mRNA level of ROCK1, RHOA, and LIMK2 as genes associated with apoptosis in evaluation of effectiveness of adalimumab treatment

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