The Janus Faces of IL-6 in GN

Abstract

various miR, and miR-21 is one of the most intensively studied miR regulated by HIF-1. 11 The complex network of HIF-1 and miR is a critical subject for future studies.PTEN is also known to be involved in a network of interactions with p53, which transcriptionally activates genes involved in cell cycle control and apoptosis. PTEN regulates p53 protein levels and transcriptional activity through both phosphatase dependent and independent mechanisms. A crucial role of p53 in tubules damaged by ischemia reperfusion has been reported by the authors' group and others, 12-14 and a role of p53 in the HIF-1/miR-687/PTEN signaling pathway is an important issue to be pursued.Finally, hypoxia is a condition of energy depletion caused by disturbance of aerobic respiration of mitochondria. HIF-1 plays a critical role in energy metabolism, reprogramming cellular metabolism toward enhanced glycolysis and reduced oxidative phosphorylation (i.e., Warburg effect). Recent studies clarified the functional role of HIF-1-induced large intergenic ncRNA-p21 (lincRNA-p21) in this metabolic reprogramming. LincRNA-p21 is rapidly induced by HIF-1a, and lincRNA-p21 then disrupts the HIF-1a von Hippel-Lindau interaction, stabilizes HIF-1a, and increases expression of HIF-1a-responsive genes (e.g., glycolytic enzymes Glut1 and LDHA), thereafter promoting glycolysis and reprogramming cellular metabolism. 15 Regulation of energy metabolism by the HIF-1/miR-687/PTEN signaling pathway should be investigated in the future.This study is well-conducted with sophisticated techniques, validating the observations using independent methodologies from various aspects. Thomas Edison gave us the aphorism "Everything comes to him who hustles while he waits" that emphasizes the importance of the energetic and ongoing pursuit of a given goal. The work of Bhatt and colleagues is a wonderful example of how the vigorous and unremitting exploration of mechanisms underlying acute ischemic injury can lead to rewarding insights, including those, as shown in this study, regarding miR-687 and HIF delineation of the novel HIF-1/miR-687/PTEN signaling pathway providing new insights into the understanding of the pathogenesis of AKI to develop novel therapeutic approaches. The Janus Faces of IL-6 in GN Alan D. Salama* and Mark A. Little †

Tocilizumab monotherapy uncovered the role of the CCL22/17‐CCR4+ Treg axis during remission of crescentic glomerulonephritis

“…The effect of IL-6 blockade on this murine cGN model remains controversial. 20,25,26 In our model, an Il-6 À/À background reduced disease severity (Supplementary figure 4a and b). Furthermore, anti-IL-6R antibody (MR16-1) treatment at the early phase ameliorated pathological results (Supplementary figure 5a and b).…”

“…The effect of IL‐6 blockade on this murine cGN model remains controversial 20,25,26 . In our model, an Il‐6 −/− background reduced disease severity (Supplementary figure 4a and b).…”

A combinational approach to restore cytokine balance and to inhibit virus growth may promote patient recovery in severe COVID-19 cases

“…Macrophage activation and polarization are also found to be correlated with IL-6 and its receptor. M1 macrophages are responsible for amplifying the inflammatory feedback loop whereas M2 macrophages are anti-inflammatory and therefore critical to establishing metabolic control and tissue homeostasis [29] , [30] . Studies have shown that blockade of IL-6R function positively correlates with activation of M1 macrophages as well as with IL-6 trans-signaling-mediated pro-inflammatory responses.…”