Inflammation Transition Research Articles

Loss of FUT8 in renal tubules ameliorates ischemia-reperfusion injury-induced renal interstitial inflammation transition to fibrosis via the TLR3-NF-κB pathway.

Renal ischemia-reperfusion injury (IRI) is a common reason of acute kidney injury (AKI). AKI can progress to chronic kidney disease (CKD) in some survivors. Inflammation is considered the first-line response to early-stage IRI. We previously reported that core fucosylation (CF), specifically catalyzed by α-1,6 fucosyltransferase (FUT8), exacerbates renal fibrosis. However, the FUT8 characteristics, role, and mechanism in inflammation and fibrosis transition remain unclear. Considering renal tubular cells are the trigger cells that initiate the fibrosis in the AKI-to-CKD transition in IRI, we targeted CF by generating a renal tubular epithelial cell (TEC)-specific FUT8 knockout mouse and measured FUT8-driven and downstream signaling pathway expression and AKI-to-CKD transition. During the IRI extension phase, specific FUT8 deletion in the TECs ameliorated the IRI-induced renal interstitial inflammation and fibrosis mainly via the TLR3 CF-NF-κB signaling pathway. The results firstly indicated the role of FUT8 in the transition of inflammation and fibrosis. Therefore, the loss of FUT8 in TECs may be a novel potential strategy for treating AKI-CKD transition.

RARE COMPLICATION OF CROHN’S DISEASE WITH LOCALIZATION IN THE INFLAMMATORY INTESTINE IN THE F0ORM OF THE SPREAD OF INFLAMMATORY OF THE PROCESS ON THE ANTERIOR ABDOMINAL WALL WITH FORMATION ABSCESS AND ITS DISCLOSURE IN THE NAVEL

The purpose of the study. Show a rare variant of the clinical course of complications of Crohn’s disease (СD). To analyze the anamnestic data, symptoms, clinical manifestations, preoperative diagnosis, features of surgery, postoperative period and the results of histological examination in a patient with CD who had complications in the form of transition of inflammation from the ileal wall to the anterior abdominal wall with abscess formation, opening it in the navel and the formation of a fistula.
 Material and methods. An analysis of the case of a complicated course of CD, manifested by the transition of inflammation from the ileum to the anterior abdominal wall, the formation of an abscess, its breakthrough into the navel and the formation of a fistula in the umbilical region. This complication was detected only after urgent computed tomography of the abdominal cavity and small pelvis (CTACSP).
 Results. The patient, despite the history of complaints, performed appendectomy, in which the removed appendix did not fully correspond to the clinical manifestations and data of CTACSP, in which CD was suspected, did not complete the examination, was not consulted by gastroenterologists and proctologists. He was urgently hospitalized with a clinic similar to acute purulent omphalitis. Only careful collection of the anamnesis and performance of urgent CTACSP allowed to suspect existence at the patient of the complicated course of CD. This allowed us to predict the course of surgery, perform a right hemicolectomy with excision of the altered tissues of the anterior abdominal wall and suturing the wound in the form of a laparostomy. The patient’s condition improved, he was discharged from the hospital.
 Conclusions. Patients with suspected CD should be monitored and treated by gastroenterologists and proctologists. Careful collection of anamnesis in patients of this group and the implementation of emergency CTACSP allowed to establish a correct diagnosis in the preoperative period.

ACTIVITY OF ANGIOTENSIN-CONVERSING ENZYME-2 IN ACUTE PULMONARY INFLAMMATION

Relevance. Angiotensin converting enzyme-2 (ACE2), which is the gateway to coronavirus, is also an important component of the tissue renin-angiotensin system with a number of anti-inflammatory effects. It is known that ACE2 is expressed in the lungs of patients with coronavirus pneumonia, but it is not clear how this depends on the stages of development and the severity of inflammation.
 Objective: to establish the effect of acute inflammation on pulmonary expression of angiotensin-converting enzyme-2.
 Material and methods. In Wistar rats (n=20), in compliance with bioethical standards, a sterile nylon thread 2.5 cm long and 0.2 mm thick to a depth of 2.5 cm was introduced into the trachea. The animals were observed and removed from the experiment at 7, 14, 21 and 28 days, microscopic and immunohistochemical (monoclonal antibodies against ACE2; clone 4G5.1; EMD Millipore Corporation; Temecula, CA US) studies were performed.
 Results. The microscopic picture of the lungs indicated the development of acute bronchopulmonary inflammation during the first week, the formation of peribronchial and alveolar abscesses in the second week with the onset of resolution of bronchopneumonia with the organization of abscesses in the third week and the development of diffuse fibrosis of the parenchyma and vascular hyalinosis in the fourth week of observation. The exudative phase of acute inflammation was accompanied by inhibition of ACE2 activity in bronchial epithelial cells, type II alveolocytes and vascular endothelium. With the transition of inflammation to the stage of proliferation and fibrosis, ACE2 activity was restored.
 Conclusion. The detected phase change in ACE2 activity can cause a wavy recurrent course of coronavirus infection, since an increase in the amount of ACE2 protein during attenuation of acute inflammation contributes to an increase in target cell infection.

ПЕРСПЕКТИВЫ ИСПОЛЬЗОВАНИЯ РАДИОНУКЛИДНЫХ МЕТОДОВ ИССЛЕДОВАНИЯ ДЛЯ ДИАГНОСТИКИ И ОЦЕНКИ ЭФФЕКТИВНОСТИ ЛЕЧЕНИЯ ПОСЛЕДСТВИЙ ПЕРЕНЕСЕННОЙ НОВОЙ КОРОНАВИРУСНОЙ ИНФЕКЦИИ

Purpose: to determine the role of nuclear medicine methods in the diagnosis and quality control of treatment and rehabilitation of patients with complications after coronavirus diseasr (COVID-19)
 The article provides a brief analysis of the incidence of COVID-19 and highlights the role of diagnosis, treatment and rehabilitation of patients suffering from the consequences of coronavirus diseasr after the end of the pandemic. The most common clinical manifestation of coronavirus diseasr is bilateral interstitial pneumonia, one of the complications of which is the development of acute respiratory distress syndrome, its pathogenesis is highlighted. It is also noted that the leading link in the development of the disease is a systemic lesion of the endothelial vascular wall, which is the cause of thrombosis and its complications, primarily pulmonary embolism, ischemic brain infarctions and cardiovascular catastrophes. 
 Specific methods of radionuclide diagnostics are described for individual organs and systems: respiratory, cardiovascular, brain, and others. The need to diagnose and control the quality of treatment and rehabilitation of patients with post-inflammatory changes in the parenchyma of internal organs and a decrease in their functional ability due to sclerotic changes, patients with changes in the state due to the transition of inflammation to the chronic stage, as well as with an overactive immune response to inflammatory changes.
 Conclusion: at the stage of diagnosis and treatment of the consequences of a previous coronavirus diseasr and subsequent rehabilitation, molecular imaging methods are essential in a complex of studies.

Sequential IL-23 and IL-17 and increasedMmp8andMmp14expression characterize the progression of an experimental model of periodontal disease in type 1 diabetes

Molecular mechanisms responsible for periodontal disease (PD) and its worsening in type 1 Diabetes Mellitus (DM1) remain unknown. Cytokine profile and expression levels of collagenases, Mmp14, and tissue inhibitors were determined, as were the numbers of neutrophils and macrophages in combined streptozotocin-induced DM1 and ligature-induced PD models. Increased IL-23 (80-fold) and Mmp8 expression (25-fold) was found in DM1. Ligature resulted in an IL-1β/IL-6 profile, increased expression of Mmp8, Mmp13, and Mmp14 (but not Mmp1), and transient expression of Timp1 and Reck in non-diabetics. PD in DM1 involved IL-1β (but not IL-6) and IL-23/IL-17, reduced IL-6 and IL-10, sustained Mmp8 and Mmp14, increased Mmp13 and reduced Reck expression in association with 20-fold higher counts of neutrophils and macrophages. IL-23 and Mmp8 expression are hallmarks of DM1. In association with the IL-1/IL-6 (Th1) response in PD, one found a secondary IL-17 (Th17) pathway in non-diabetic rats. Low IL-6/TNF-α suggest that the Th1 response was compromised in DM1, while IL-17 indicates a prevalence of the Th17 pathway, resulting in high neutrophil recruitment. Mmp8, Mmp13, and Mmp14 expression seems important in the tissue destruction during PD in DM1. PD-associated IL-1/IL-6 (Th1), IL-10, and Reck expression are associated with the acute-to-chronic inflammation transition, which is lost in DM1. In conclusion, IL-23/IL-17 are associated with the PD progression in DM1.

Abstract 1563: Role of EGFR during the transition of inflammation to dysplasia in a colitis-associated colon cancer model

Abstract Background: The underlying mechanisms in ulcerative colitis-associated dysplasia are poorly understood. Neurokinin-1 receptors (NK-1R) have been shown to be involved in chronic colonic inflammation, and we have demonstrated their over-expression in patients with dysplasia. The NK-1R has been found to crosstalk with the epidermal growth factor receptor (EGFR). EGFR is related to the development of some cancers including colorectal cancer. Erlotinib, a potent inhibitor of the EGFR tyrosine kinase, has been shown to inhibit the intracellular EGFR signaling pathway and to block non-small cell lung cancer and pancreatic tumor growth; however its role in the genesis of dysplasia is unknown. Aim: The aim of this study was to investigate the role of EGFR in a novel model of colitis-associated dysplasia using a small molecule inhibitor, Erlotinib. Methods: Sprague Dawley rats received trinitrobenzene sulfonic acid (TNBS; 30 mg in 50% ethanol, ic.), followed six weeks later by reactivation with TNBS (5 mg/kg, iv.) for three days. To induce colitis-associated dysplasia, the rats then received TNBS (iv.) twice a week for ten weeks. One group received the Erlotinib (10 mg/kg, ip.) for one week before the start of the reactivation of the colitis and two weeks after (21 days); the rest received the vehicle. After sacrifice, the colons were removed and analyzed for damage and expression of NK-1R, Cox-2, EGFR, and the downstream signaling components. Results: Animals receiving Erlotinib had no significant difference in macroscopic or microscopic damage from controls. Pathological analysis however revealed a decrease of the incidence of dysplasia in animals treated with Erlotinib when compared with the vehicle-treated animals. This decrease was most evident in both the mid and the distal colon (15% vs. 53% and 20% vs. 61%). Colonic tissues from Erlotinib-treated animals also had decreased expression of NK-1R, Cox-2, pErk ½, and Akt compared to the vehicle-treated group. Conclusion: Our results suggest that Erlotinib can delay the development of colitis associated dysplasia, suggesting a potential therapeutic use for Erlotinib in patients with long-standing colitis. Supported in part by 1U56 CA126379-01 and 1F31 GM078951. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 1563.