Article of the Year 2021
COVID-19 and Toll-Like Receptor 4 (TLR4): SARS-CoV-2 May Bind and Activate TLR4 to Increase ACE2 Expression, Facilitating Entry and Causing HyperinflammationRead the full article
Mediators of Inflammation publishes papers on all types of inflammatory mediators, including cytokines, histamine, bradykinin, prostaglandins, leukotrienes, PAF, biological response modifiers and the family of cell adhesion-promoting molecules
Chief Editor, Professor Agrawal, is an Assistant Clinical Professor of the Division of Basic and Clinical Immunology. Dr. Agrawal's research focuses on the dendritic cells of the immune system in the context of aging and autoimmunity.
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Treatment with Herbal Formula Extract in the hSOD1G93A Mouse Model Attenuates Muscle and Spinal Cord Dysfunction via Anti-Inflammation
Amyotrophic lateral sclerosis (ALS), a multicomplex neurodegenerative disease, has multiple underlying pathological factors and can induce other neuromuscular diseases, leading to muscle atrophy and respiratory failure. Currently, there is no effective drug for treating patients with ALS. Herbal medicine, used to treat various diseases, has multitarget effects and does not usually induce side effects. Each bioactive component in such herbal combinations can exert a mechanism of action to increase therapeutic efficacy. Herein, we investigated the efficacy of an herbal formula, comprising Achyranthes bidentata Blume, Eucommia ulmoides Oliver, and Paeonia lactiflora Pallas, in suppressing the pathological mechanism of ALS in male hSOD1G93A mice. Herbal formula extract (HFE) (1 mg/g) were orally administered once daily for six weeks, starting at eight weeks of age, in hSOD1G93A transgenic mice. To evaluate the effects of HFE, we performed footprint behavioral tests, western blotting, and immunohistochemistry to detect protein expression and quantitative PCR to detect mRNA levels in the muscles and spinal cord of hSOD1G93A mice. HFE-treated hSOD1G93A mice showed increased anti-inflammation, antioxidation, and regulation of autophagy in the muscles and spinal cord. Thus, HEF can be therapeutic candidates for inhibiting disease progression in patients with ALS. This study has some limitations. Although this experiment was performed only in male hSOD1G93A mice, studies that investigate the efficacy of HEF in various ALS models including female mice, such as mice modeling TAR DNA-binding protein 43 (TDP43) and ORF 72 on chromosome 9 (C9orf72) ALS, are required before it can be established that HEF are therapeutic candidates for patients with ALS.
The mir-21 Inhibition Enhanced HUVEC Cellular Viability during Hypoxia-Reoxygenation Injury by Regulating PDCD4
The purpose of this study was to explore the clinical value of altered plasma mir-21 expression level as a biomarker for the severity of coronary artery disease (CAD) and its molecular impact on HUVEC cellular injuries. Angiographically validated 56 patients with single-vessel CAD disease, 92 patients with double-vessel CAD, 139 complex coronary artery stenosis patients, and 56 healthy individuals () were enrolled in this study. The expressions of plasma mir-21 were evidently and progressively higher while PDCD4 levels were significantly and steadily lower in single-, dual-, and multivessel occluded CAD patients than in healthy participants (). The relative expressions of mir-21 in hypoxia-reoxygenation- (HR-) exposed HUVECs were markedly upregulated, but PDCD4 concentrations were obviously downregulated as compared with normal control cells (). Moreover, altered circulatory mir-21 expression levels were able to significantly differentiate single- (AUC 0.893), double- (AUC 0.914), and multivessel stenosis CAD (AUC 0.933) patients from healthy subjects. Besides, the plasma mir-21 expressions in elderly (66-85 years) groups were remarkably higher than those in younger aged (25-45 years) subjects. Caspase-3 and ROS expression levels were remarkably elevated, but cellular viability noticeably declined in HR-induced HUVECs than in normoxic cells (). In contrast, mir-21 inhibition markedly reduced caspase-3 activity and ROS concentrations while significantly ameliorating HUVEC cellular viability in HR conditions. PDCD4 expressions in HR-exposed HUVECs were prominently decreased whereas mir-21 inhibition significantly enhanced PDCD4 levels (). Upregulated plasma mir-21 can be a valuable clinical biomarker for the detection of the severity of coronary artery stenosis patients. Elevated circulatory mir-21 concentrations have a positive correlation with aging. Inhibitory mir-21 evidently increased HUVEC cellular viability through upregulation of targeting PDCD4 and recommended a newer possible therapeutic molecule for the management of CAD patients.
White Blood Cell Count and Serum Cytokine Profile in Tropical Hardwood Workers in Kumasi
Background. Occupational exposure to wood dust particles has long been reported of its associated varying degrees of negative health effects due to different extractive chemicals present in the various timber species. However, tropical hardwood is also reported to have higher levels of extractive chemicals of antihistamine, antioxidant, and anti-inflammatory properties. In Ghana, woodworkers have for years been exposed to wood dust from mixed tropical hardwood species, with little or no protective equipment such as nose masks, yet with less significant respiratory conditions. This study seeks to investigate the serum cytokine profile in tropical hardwood workers in Kumasi to provide a better understanding of the immunoregulatory pattern activated in the woodworkers. Method. The study was carried out among woodworkers, teachers, and security men located in Kumasi. A cross-sectional sampling of adult male workers was selected to participate in the study (86 woodworkers and 89 nonwoodworkers). Participants donated blood collected by venepuncture into EDTA tubes and spun to separate serum for cytokine assay. Cytokines including IFN-gamma, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL-13, and IL-17 were assayed using the Human Premixed Multianalyte Kit (R&D System, Inc., Minneapolis, USA) following the manufacturer’s procedure. The cytokine levels were quantified using the Luminex200 analyser. Results. The mean concentration levels for the various cytokines were significantly different () between woodworkers and nonwoodworkers except IL-2. There were significantly increased levels of Th1 and Th2 cytokines expressed in the woodworkers more than the nonwoodworkers. Conclusions. The results from this study reveal that exposed woodworkers of mixed tropical hardwood species show a high level of Th1 and Th2 cytokines in their serum than nonwoodworkers.
Enriched Environment-Induced Neuroprotection against Cerebral Ischemia-Reperfusion Injury Might Be Mediated via Enhancing Autophagy Flux and Mitophagy Flux
Background. Enriched environment (EE) can protect the brain against damages caused by an ischemic stroke; however, the underlying mechanism remains elusive. Autophagy and mitochondria quality control are instrumental in the pathogenesis of ischemic stroke. In this study, we investigated whether and how autophagy and mitochondria quality control contribute to the protective effect of EE in the acute phase of cerebral ischemia–reperfusion injury. Methods. We exposed transient middle cerebral artery occlusion (tMCAO) mice to EE or standard condition (SC) for 7 days and then studied them for neurological deficits, autophagy and inflammation-related proteins, and mitochondrial morphology and function. Results. Compared to tMCAO mice in the SC group, those in the EE group showed fewer neurological deficits, relatively downregulated inflammation, higher LC3 expression, higher mitochondrial Parkin levels, higher mitochondrial fission factor dynamin-related protein-1 (Drp1) levels, lower p62 expression, and lower autophagy inhibitor mTOR expression. Furthermore, we found that the EE group showed a higher number of mitophagosomes and normal mitochondria, fewer mitolysosomes, and relatively increased mitochondrial membrane potential. Conclusion. These results suggested that EE enhances autophagy flux by inhibiting mTOR and enhances mitophagy flux via recruiting Drp1 and Parkin to eliminate dysfunctional mitochondria, which in turn inhibits inflammation and alleviates neurological deficits. Limitations. The specific mechanisms through which EE promotes autophagy and mitophagy and the signaling pathways that link them with inflammation need further study.
Magnoliae flos Downregulated Lipopolysaccharide-Induced Inflammatory Responses via NF-κB/ERK-JNK MAPK/STAT3 Pathways
Background. Magnoliae flos is the dried flower bud of Magnolia biondii and related plants. It has been used as a medicinal herb for the treatment of rhinitis, sinusitis, and sinus headaches. Nevertheless, the effects of Magnoliae flos in microbial infection or sepsis remain unclear. In this study, we investigated the anti-inflammatory effects of Magnoliae flos water extract (MF) in lipopolysaccharide- (LPS-) induced septic mice and LPS-stimulated RAW264.7 macrophages. Results. We found that MF reduced the mortality of LPS-challenged mice. Enzyme immunoassays and reverse transcription polymerase chain reaction analysis revealed that MF administration attenuated mRNA expression and protein production of proinflammatory mediators, including cyclooxygenase 2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. In parallel to these results in mice, pretreatment with MF suppressed the LPS-induced production of proinflammatory mediators in RAW264.7 macrophages. In addition, we found that MF exerted its suppressive effects by inhibiting the activation of the mitogen-activated protein kinase, nuclear factor-κB, and signal transducer and activator of transcription pathways at the protein level. Conclusion. MF could be a potential therapeutic agent for regulating excessive inflammatory responses in sepsis.
The Gut Microbiota Dysbiosis in Preeclampsia Contributed to Trophoblast Cell Proliferation, Invasion, and Migration via lncRNA BC030099/NF-κB Pathway
Background. Preeclampsia (PE) is the main reason of maternal and perinatal morbidity and mortality. Gut microbiota imbalance in PE patients is accompanied by elevated serum lipopolysaccharide (LPS) levels, but whether it affects the occurrence and development of PE, the underlying mechanism is not clear. This paper intends to investigate the relationship between lncRNA BC030099, inflammation, and gut microbiota in PE. Methods. The feces of the patients were collected, and gut microbiota changes were assessed by 16S rRNA sequencing and pathway analysis by PICRUSt. Next, we examined LPS and lncRNA BC030099 levels in feces or placenta of PE patients. Then, we knocked down lncRNA BC030099 in HTR-8/SVneo cells and added the NF-κB pathway inhibitor JSH-23. CCK-8 and Transwell assays were performed to determine cell proliferation, migration, and invasion. Western blot was utilized to evaluate MMP2, MMP9, snail, and E-cadherin, p-IκBα, IκBα, and nuclear NF-κB p65 levels. IL-6, IL-1β, and TNF-α levels were examined by ELISA. Results. Gut microbiota was altered in PE patients, and microbial genes associated with LPS biosynthesis were significantly elevated in gut microbiota in the PE group. LPS level in feces and placenta of PE group was significantly elevated. lncRNA BC030099 level in placenta of PE group was also notably promoted. Knockdown of lncRNA BC030099 promoted HTR-8/SVneo cell proliferation, migration, and invasion. Knockdown of lncRNA BC030099 also elevated MMP2, MMP9, and snail levels and repressed E-cadherin level. In addition, lncRNA BC030099 affected NF-κB pathway. Furthermore, NF-κB inhibitor reversed HTR-8/SVneo cell proliferation, invasion, and migration induced by LPS. Conclusions. The gut microbiota dysbiosis in PE contributed to HTR-8/SVneo cell proliferation, invasion, and migration via lncRNA BC030099/NF-κB pathway.