A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors

Kaur, Sukhvir; Bansal, Yogita; Kumar, Raj; Bansal, Gulshan

doi:10.1016/j.bmc.2020.115327

Cited by 244 publications

(205 citation statements)

References 151 publications

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“…IL-6 is a lymphokine produced by activated T cells and fibroblasts, which can make B cell precursors become antibody producing cells. In collaboration with colony stimulating factor, IL-6 can promote the growth and differentiation of original bone marrow-derived cells and enhance the lysis function of natural killer cells [33]. IL-23 is released from antigen presenting cells and induces expansion of Th17 cells and is necessary for their maintenance, thus forming the IL-23/IL-17 axis [34].…”

Section: Discussionmentioning

confidence: 99%

Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

et al. 2020

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Background: Increased leucine-rich α2-glycoprotein-1 (LRG1) has been observed in various inflammatory and autoimmune diseases. We aimed to explore the expression and role of LRG1 in lupus nephritis (LN). Methods: Plasma LRG1 (pLRG1) was measured by enzyme-linked immunosorbent assay in 101 patients with renal biopsy-proven LN and 21 healthy controls (HC). Relationships between pLRG1 and clinical and pathological characteristics were analyzed. The expression of LRG1 in peripheral blood leukocytes and kidney was detected by flow cytometry, immunohistochemistry and immunofluorescence, respectively. Further cell experiments were focused on the role of LRG1.Results: We found that LRG1 was expressed in plasma, some peripheral blood leukocytes, proximal tubule and several inflammatory cells. The levels of LRG1 in plasma, peripheral blood leukocytes and kidney were elevated in LN patients as compared to HC. Plasma expression levels of LRG1 correlated positively with renal function and renal disease activity, and reflect specific pathologic lesions in the kidneys of patients with LN. Interleukin-1β and interleukin-6, not tumor necrosis factor-α and interferon γ induced the LRG1 expression in human renal tubular epithelial cell line. Moreover, stimulation of recombinant human LRG1 could inhibit late apoptosis, promote proliferation and regulate expression of inflammatory factors and cytokines. Conclusions: Plasma expression levels of LRG1 were associated with renal function, disease activity, and pathology in LN. It might also be involved in renal inflammation, proliferation and apoptosis of endothelial cells. LRG1 might be a potential prognosis novel predictor in LN patients.

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Section: Discussionmentioning

confidence: 99%

Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

et al. 2020

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“…As reported, IL-6 is an important cytokine that initially expressed through the immune system in response to injurious or infectious processes(17) [17]. In the early stage, it activates the JAK/STAT signal pathway, and initiates B cell differentiation, plasma cell production and a series of acute reactions (18,19) [18,19]. The increase of IL-6 occurs early in the initiation of cellular stress and has a long duration, so it can be used as an indicator for the early diagnosis of acute infection as well as the severity and prognosis of infection(20) [20].…”

Section: Discussionmentioning

confidence: 98%

“…Since December 2019, the large-scale spread of the new coronavirus disease (COVID- 19), o cially known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a major epidemiological event(1) [1]. As of April 14, 2020, COVID-19 has affected more than 1,948,617 patients in 210 countries and regions around the world, resulting in approximately 121,846 deaths worldwide (2,3) [2,3].…”

Section: Introductionmentioning

confidence: 99%

Uncovering the underlying mechanisms of Compound Yuxingcao Mixture in the treatment of COVID-19 based on network pharmacology

Chen¹,

Zhang²,

Yuan³

et al. 2020

Preprint

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Background and objective: The novel coronavirus named COVID-19 emerged in Wuhan, China in December, 2019 and has spread rapidly in China and around the world. The traditional Chinese medicine Compound Yuxingcao Mixture (CYM) has been recommended in recent editions of the national guideline while the underlying mechanisms are still unclear. In this study, we analyzed the effectiveness and potential mechanisms of CYM on COVID-19 based on network pharmacology and molecular docking approach. Methods: The active ingredients and potential targets of CYM were screened using TCMSP and STITCH databases. Genes related severe acute respiratory syndromes (SARS) and Middle East respiratory syndrome (MERS) were queried on the DisGeNET and MalaCards databases. CYM-COVID-19 common target protein interaction network was established by STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted to generate the relative pathways based on KOBAS databases. In addition, the possible binding site of screened compounds were also predicted by Autodock vina software. Results: A total of 103 active ingredients and 205 putative targets were screened from CYM, of which 32 overlapped with the targets of COVID-19 and were considered therapeutic targets. The analysis of the network diagram demonstrated that the CYM activity of ingredients of quercetin, luteolin, β-sitosterol and kaempferol may play a crucial role in treating COVID-19 by regulating TNF, IL-6, IL-1β, etc. The analysis of molecular binding energy showed that β-sitosterol had the lowest binding energy with COVID-19 3CLpro (-8.63 kJ/mol). GO and KEGG enrichment analysis revealed that these targets were closely associated with inflammatory responses and immune defense processes. Conclusion: In summary, our study identified the potential mechanisms and targets of CYM for the prevention of COVID-19, providing directions for further clinical research.

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“…It can activate JAK/STAT signal pathway in the early stage, regulate B cell differentiation, plasma cell generation and a series of acute phase reactions. IL-6 plays a key role in the acute in ammatory response [23], mainly accelerating the alveolar in ammatory response in the early stage of pulmonary brosis through chemotactic in ammatory cell aggregation and promoting in ammatory cell in ltration And then it can mediate the occurrence of idiopathic pulmonary brosis and damage the lung [24], which can be used as the initial diagnosis of infectious diseases. Mitogen-Activated Protein Kinase (MAPK) family members MAPK1, MAPK3, MAPK8 are activated under oxidative stress, viral infection, cancer, etc.…”

Section: Discussionmentioning

confidence: 99%

The Mechanism of Prevention and Treatment of Maxing Shigan Decoction on Pulmonary Heart Injury Caused by Novel Coronavirus Pneumonia

Liu

Hou

et al. 2020

Preprint

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Background To explore the mechanism of Maxing Shigan Decoction in the treatment of myocardial injury and lung injury through network pharmacology and molecular docking technology. Methods In Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), a Bioinformatics Analysis Tool for Molecular mechANism of Traditional Chinese Medicine (BATMAN-TCM) and the Comparative Toxicogenomics Database, National Center for Biotechnology Information database, Online Mendelian Inheritance in Man database, the compounds and targets of each drug in Maxing Shigan Decoction and the targets of “acute lung intervention” and “myocardial injury” diseases were searched. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed by the DAVID database. GOLD 5.1 was used for molecular docking. Results Maxing Shigan Decoction includes 327 compounds and 2722 targets, including 30 key targets. 2125 items were obtained by GO enrichment analysis, including 2047 items of Biological Process, 28 items of Cell Composition and 50 items of Molecular Function. The KEGG pathway was enriched to obtain 149 pathways. The results of molecular docking showed that Gancaonin H and Licorice Glycoside E were well combined with Angiotensin-Converting Enzyme 2-A (ACE2-A) and Angiotensin-Converting Enzyme 2-B (ACE2-B), respectively, and Licorice was well combined with Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF) and Interleukin 6 (IL-6). Supraene is an active compound of Ephedra. It has good binding with ACE2-A, ACE2-B, GM-CSF and IL-6, respectively. (6Z, 10E, 14E, 18E)-2, 6, 10, 15, 19, 23- hexamethyletracosa-2, 6, 10, 14, 18, 22- hexaene are the active compounds of Almond, which are well combined with ACE2-A, ACE2-B, GM-CSF and IL-6. Conclusion Maxing Shigan Decoction may act on ACE2, GM-CSF and IL-6 targets through the active compounds Supraene of Ephedra, and Almond (6Z, 10E, 14E, 18E)-2, 6, 10, 15, 19, 23-hexamethyletracosa-2, 6, 10, 14, 18, 22-hexaene. Gancainin H and licorice Glycide E are the active compounds of Licorice, act on A and B sites of ACE2 respectively, and Glycyrin acts on GM-CSF and IL-6 targets, coordinating multiple signal pathways to play anti-inflammatory and antiviral roles to prevent and treat lung and heart injury caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).

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A panoramic review of IL-6: Structure, pathophysiological roles and inhibitors

Cited by 244 publications

References 151 publications

Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

Leucine-rich α2-glycoprotein-1 upregulation in plasma and kidney of patients with lupus nephritis

Uncovering the underlying mechanisms of Compound Yuxingcao Mixture in the treatment of COVID-19 based on network pharmacology

The Mechanism of Prevention and Treatment of Maxing Shigan Decoction on Pulmonary Heart Injury Caused by Novel Coronavirus Pneumonia

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