Transforming growth factorβ1 (TGF-β1) is the main modulator of the healing process after tissue injury. In the kidney, if TGF-β1 release is not switched off, extracellular matrix components (ECM) are accumulated and tissue fibrosis occurs. Urinary TGF-β1 levels reflect its renal production and it has been determined in various types of glomerular disease. In this review, a critical analysis of the different immunoassays that have been used for the measurement of TGF-β1 in the urine is presented and the importance of the serial determination of urinary TGF-β1 levels in patients with various types of renal disease is discussed.

A newly identified virus appeared in Wuhan, China, in December 2019, was named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and caused the coronavirus disease 2019 (COVID-19). SARS-CoV-2 presents similarities with two previous coronavirus pandemics, MERS (Middle East Respiratory Syndrome) and SARSCoV, concerning phylogenetic origin, structural composition, and clinical symptoms, thus, leading to common pathogenic mechanisms. The purpose of this review is to declare the role of interleukin-6 (IL-6) in the pathogenesis, prognosis, and treatment of COVID-19 by comparing its effect on SARS-CoV and MERS cases. Increased levels of IL-6 comprise the key for the stimulation of cytokine storm and the progression of SARS, MERS, and COVID-19 cases. Especially, in COVID-19 patients, the overactivation of NF-kΒ, which is caused by the binding of coronavirus spike protein S to alveolar epithelial cells, up-regulates IL-6 and promotes its systematic circulation, causing alveolar damage and extrapulmonary injury. Additionally, IL-6 can be used to evaluate respiratory failure and identify asymptomatic patients. Tocilizumab (TCZ), a monoclonal antibody which blocks IL-6 signaling, comprises a remedial option against COVID-19. TCZ improves oxygenation, reduces fever, and decreases levels of IL-6. IL-6 plays a major role in the pathogenesis of cytokine storm and the progression of COVID-19 and may be used as a therapeutic target against COVID-19. However, further research is needed concerning the relation of IL-6 in COVID-19 cases, and more clinical trials are required to declare TCZ as a treatment option.

Crescentic nephritis is characterized by formation of cellular crescents that soon become fibrotic and result in irreversible damage, unless an effective immunosuppressive therapy is rapidly commenced. TGF-β₁ is involved in the development of crescents through various pathways. The aim of this study was to identify whether the determination of urinary TGF-β₁ levels in patients with crescentic nephritis could be used as a marker of response to treatment. Fifteen patients with crescentic nephritis were included in the study. The renal expression of TGF-β₁ was estimated in biopsy sections by immunohistochemistry and urinary TGF-β₁ levels were determined by quantitative sandwich enzyme immunoassay (EIA). TGF-β₁ levels were determined at the time of renal biopsy, before the initiation of immunosuppressive treatment (corticosteroids, cyclophosphamide and plasma exchange). Twelve patients with other types of proliferative glomerulonephritis and ten healthy subjects were used as controls. Improvement of renal function with immunosuppressive therapy was observed in 6 and stabilization in 4 patients (serum creatinine from 3.2 ± 1.5 to 1.4 ± 0.1 mg/dl and from 4.4 ± 1.2 to 4.1 ± 0.6 mg/dl, respectively). In 5 patients, with severe impairment of renal function who started on dialysis, no improvement was noted. The main histological feature differentiating these 5 patients from others with improved or stabilized renal function was the percentage patients with poor response to treatment were the percentage of glomeruli with crescents and the presence of ruptured Bowman's capsule and glomerular necrosis. Urinary TGF-β₁ levels were significantly higher in patients who showed no improvement of renal function with immunosuppressive therapy (930 ± 126 ng/24 h vs. 376 ± 84 ng/24 h, p < 0.01). TGF-β₁ was identified in crescents and tubular epithelial cells, whereas a significant correlation of TGF-β₁ immunostaining with the presence of fibrocellular cresents was observed (r = 0.531, p < 0,05). Increased TGF-β₁ renal expression and urinary excretion that is related to the response to immunosuppressive therapy was observed in patients with crescentic nephritis. Evaluation of urinary TGF-β₁ levels may be proved a useful marker of clinical outcome in patients with crescentic nephritis.

Hydrogen peroxide (Η2Ο2) is produced during a variety of cellular procedures. In this paper, the regulatory role of Η2Ο2, in Escherichia coli phagocytosis by the human polymorphonuclears, was investigated. White blood cells were incubated with dihydrorhodamine (DHR) in order to study H2O2 synthesis and E. coli-FITC to study phagocytosis. Flow cytometry revealed increased synthesis of H2O2 in polymorphonuclears which incorporated E. coli-FITC. The blocking of H2O2 synthesis by specific inhibitors, N-ethylmaleimide (ΝΕΜ) for NADPH oxidase and diethyldithiocarbamate (DDC) for superoxide dismutase (SOD), decreased E. coli phagocytosis, as well. Immunoblot analysis of white blood cell protein extracts revealed that the blocking of NADPH oxidase and SOD decreased ERK-1/2 phosphorylation, while it had no effect on JNK and p38. Confocal microscopy showed that phosphorylation of MAPKs and phagocytosis solely occur in the polymorphonuclear and not in mononuclear cells. The use of specific MAPKs inhibitors showed that all of them are necessary for phagocytosis, but only phospho-p38 affects H2O2 synthesis. The blocking of JNK phosphorylation, in the presence of E. coli, evoked a further decrease of cytoplasmic p47 thus increasing its translocation onto the plasma membrane for the assembly of NADPH oxidase. It appears that newly synthesised H2O2 invigorates the phosphorylation and action of ERK-1/2 in E. coli phagocytosis, while phospho-JNK and phospho-p38 appear to regulate H2O2 production.

Background. Apoptosis, a gene‐directed form of cell death, has been involved in the resolution of renal injury but also in the development of scarring. Bcl‐2 and bax are proteins related to apoptotic process that either provides a survival advantage to rapidly proliferating cells (bcl‐2) or promote cell death by apoptosis (bax). Various cytokines and growth factors are involved in this process. This study investigates the expression of bcl‐2 and bax and the presence of apoptotic bodies in relation to the TGF‐β₁ expression at the time of diagnosis in the renal biopsies of patients with glomerulonephritis (GN). Methods. Fifty patients with various types of GN and ten controls were included in the study. Bcl‐2, bax and Transforming Growth Factor (TGF‐β₁) positive cells were detected in kidney biopsies by immunohistochemistry, while apoptotic cells were detected by in situ end labeling of fragmented DNA (ISEL). Morphometric analysis was used for quantitation of immunostaining. Results. The intensity of bcl‐2, bax and TGF‐β₁ immunostaining in the renal tissue of patients with GN was significantly more to the observed in the control biopsies. Bcl‐2 and bax were expressed within the epithelial cells of proximal, distal and collecting tubules and in the renal interstitium. Bax and bcl‐2 proteins were also identified within the glomeruli in a few patients but their distribution was not related to the type of GN. TGF‐β₁ was expressed in the cytoplasm of tubular epithelial cells and to a lesser extent in the renal interstitium and glomeruli. A positive correlation of TGF‐β₁ with the extent of bax immunostaining (r = 0.498, p < 0.05) and an inverse correlation with that of bcl‐2 (r = − 0.490, p < 0.05) were identified. Apoptotic bodies were identified only in the renal tissue of patients with GN and were mainly localized among tubular epithelial and interstitial cells. Conclusion. The intensity of bcl‐2 and bax proteins expression and the presence of apoptotic bodies in the renal tissue of patients with GN suggest that apoptotic process is ongoing during the evolution of renal disease. The correlation of TGF‐β₁ expression with that of apoptosis‐related proteins might represent an implication of this growth factor with apoptotic process in the human diseased kidney.