Anti-Inflammatory and Antioxidant Activities of the Methanolic Extract of Cyrtocarpa procera Bark Reduces the Severity of Ulcerative Colitis in a Chemically Induced Colitis ModelRead 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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Enhanced Wound Healing- and Inflammasome-Associated Gene Expression in TNFAIP3-Interacting Protein 1- (TNIP1-) Deficient HaCaT Keratinocytes Parallels Reduced Reepithelialization
TNIP1 protein is a widely expressed, cytoplasmic inhibitor of inflammatory signaling initiated by membrane receptors such as TLRs which recognize pathogen-associated and damage-associated molecular patterns (PAMPs and DAMPs). Keratinocyte TNIP1 deficiency sensitizes cells to PAMPs and DAMPs promoting hyperresponsive expression and secretion of cytokine markers (e.g., IL-8 and IL-6) relevant to cases of chronic inflammation, like psoriasis, where TNIP1 deficiency has been reported. Here, we examined the impact of TNIP1 deficiency on gene expression and cellular responses (migration and viability) relevant to acute inflammation as typically occurs in wound healing. Using siRNA-mediated TNIP1 expression knockdown in cultured HaCaT keratinocytes, we investigated TNIP1 deficiency effects on signaling downstream of TLR3 agonism with low-concentration poly (I:C), a representative PAMP/DAMP. The combination of TNIP1 knockdown and PAMP/DAMP signaling disrupted expression of specific keratinocyte differentiation markers (e.g., transglutaminase 1 and involucrin). These same conditions promoted synergistically increased expression of wound-associated markers (e.g., S100A8, TGFβ, and CCN2) suggesting potential benefit of increased inflammatory response from reduced TNIP1 protein. Unexpectedly, poly (I:C) challenge of TNIP1-deficient cells restricted reepithelialization and reduced cell viability. In these cells, there was not only increased expression for genes associated with inflammasome assembly (e.g., ASC, procaspase 1) but also for A20, a TNIP1 partner protein that represses cell-death signaling. Despite this possibly compensatory increase in A20 mRNA, there was a decrease in phospho-A20 protein, the form necessary for quenching inflammation. Hyperresponsiveness to poly (I:C) in TNIP1-deficient keratinocytes was in part mediated through p38 and JNK pathways. Taken together, we conclude that TNIP1 deficiency promotes enhanced expression of factors associated with promoting wound healing. However, the coupled, increased potential priming of the inflammasome and reduced compensatory activity of A20 has a net negative effect on overall cell recovery potential manifested by poor reepithelialization and viability. These findings suggest a previously unrecognized role for TNIP1 protein in limiting inflammation during successful progression through early wound healing stages.
Predictors for Short-Term Efficacy of Allergen-Specific Sublingual Immunotherapy in Children with Allergic Rhinitis
Background.A good compliance in allergen-specific sublingual immunotherapy (SLIT) often comes from good short-term efficacy. We aimed to evaluate the pretreatment parameters which can predict the short-term clinical efficacy in children that underwent SLIT. Methods. 517 children with allergic rhinitis (AR) that underwent SLIT were recruited in this study. Baseline clinical characteristics and laboratory parameters were collected, and the clinical efficacy was evaluated using symptom and medication scores. A multivariate logistic regression model and receiver operating characteristic (ROC) curves were established. Results. A total of 303 (65%) in 466 children that underwent SLIT achieved short-term clinical efficacy. The time of using the air conditioner was negatively correlated with clinical efficacy, whereas the serum-specific IgE (s-IgE) levels, the serum IL-10 and IL-35 levels, and the s-IgE/total-IgE ratio were positively correlated with clinical efficacy. Conclusion. The time of using the air conditioner, serum-specific IgE (s-IgE) levels, serum IL-10 and IL-35 levels, and s-IgE/total-IgE ratio may be helpful for child selection before SLIT.
Role of Mitochondrial Stress Protein HSP60 in Diabetes-Induced Neuroinflammation
Diabetes mellitus is the most common metabolic disorder characterized by hyperglycemia and associated malfunctions of the metabolism of carbohydrates, proteins, and lipids. There is increasing evidence of a relationship between diabetes and vascular dementia. Interestingly, hyperglycemia-linked neuroinflammation in the central nervous system is considered to play a key role during vascular dementia in diabetic patients. However, the mechanisms responsible for the relationship between hyperglycemia and neuroinflammation is not clearly understood. Diabetes-induced alternations in the blood-brain barrier permit high glucose influx into the brain cells via glucose transporters and promote oxidative stress through overproduction of reactive oxygen species. Despite many studies demonstrating a link between oxidative stress and mitochondrial dysfunction, the relationship between mitochondrial dysfunction and neuron inflammation during hyperglycemia remains to be established. In this review, we will focus on diabetes-induced changes in the central nervous system and the role of mitochondrial heat shock protein 60 (HSP60) as an initiator of oxidative stress and potential modulator of neuroinflammation. We suggest that oxidative stress-mediated mitochondrial dysfunction stimulates the upregulation of mitochondrial heat shock protein 60 (HSP60) and ultimately initiates inflammatory pathways by activating pattern recognition receptors. HSP60 also could be a focal point in the development of a biomarker of neuroinflammation as HSP60 is known to be significantly elevated in diabetic patients. Interestingly, extracellular secretion of HSP60 via exosomes suggests that inflammation could spread to neighboring astrocytes by activating pattern recognition receptors of astrocytes via neuronal exosomes containing HSP60. A mechanism for linking neuron and astrocyte inflammation will provide new therapeutic approaches to modulate neuroinflammation and therefore potentially ameliorate the cognitive impairment in diabetic brains associated with vascular dementia.
Density of Langerhans Cells in Nonmelanoma Skin Cancers: A Systematic Review
Langerhans cells (LCs) are bone marrow-derived dendritic cells (DCs) that represent 2-3% of the entire cell population of the human skin, known to have an ability to present antigens to T lymphocytes. Moreover, there is evidence that LCs are probably capable of inducing the local cytotoxic type T-cell-mediated response against the tumour-associated antigens. In the past two decades, a dramatic increase has been noted in the incidence of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). The purpose of this study was to critically assess the results of available studies quantitatively assessing the LCs in nonmelanoma skin cancers and try to establish a conclusion of its possible impact on their future treatment. The PubMed, EMBASE, and the Web of Science databases were searched, which returned 948 citations. After a thorough analysis of full article texts, 30 studies have been chosen, including 11 of the BCC, 12 of the SCC specimens, and 7 analysing both tumour types. There was an overall trend towards slightly higher numbers of LCs in BCC than in SCC; however, these tendencies were discrepant between the studies. We presume that such differences could be caused by various staining techniques with a broad spectrum of specificity, including anti-S100, anti-CD1a, and ATPase activity staining used for LCs identification. We hypothesise that as there is a high inconsistency between the results of the studies, as far as the densities of LCs observed in the specimens are concerned, it seems that the mechanism of the influence of LCs on the antitumoural immune response is complicated. Finally, as at present, there is a paucity of available risk scores for the recurrence or progression of BCC or SCC, the creation of classification stratifying that risk including the density of LCs could bring additional information both for the physician and the patient.
Both Low and High Postprocedural hsCRP Associate with Increased Risk of Death in Acute Coronary Syndrome Patients Treated by Percutaneous Coronary Intervention
Background. Inflammation poses dual effects after myocardial infarction, but robust evidence shows that high-sensitivity C-reactive protein (hsCRP), as an inflammatory marker, is constantly associated with worse outcomes. This study is aimed at investigating the probable nonlinear association between postprocedural hsCRP and mortality in patients with acute coronary syndromes (ACS) treated by percutaneous coronary intervention (PCI). Methods. A total of 3940 consecutive ACS patients treated by PCI with postprocedural hsCRP measurements were retrospectively recruited. Patients were stratified into 5 groups according to quintiles of hsCRP. Cox regression with adjustments for multiple covariates was used for outcome analysis. Restricted cubic spline (RCS) analysis was used to allow possible nonlinear associations. The primary outcome was all-cause death. Results. During a median follow-up of 727 days, mortality occurred in 207 (5.3%) patients. Adjusted hazard ratio (HR) was higher in the lowest (<2.26 mg/L, HR: 1.90, 95% confidence interval (CI): 1.08-3.33; ), second highest (10.16-12.56 mg/L, HR: 1.86, 95% CI: 1.09-3.16; ), and highest quintiles (≥12.56 mg/L, HR: 2.02, 95% CI: 1.21-3.36; ) of postprocedural hsCRP, compared to the second lowest quintile (2.26-4.85 mg/L). RCS analysis depicted a J-shaped association between postprocedural hsCRP and mortality (). Similar association was observed between hsCRP and cardiac death (), but not for noncardiac mortality (). Conclusions. Both low and high postprocedural hsCRP were associated with higher risk of death in ACS patients treated by PCI.
Decreased Plasma Maresin 1 Concentration Is Associated with Diabetic Foot Ulcer
Aims. To assess the maresin 1 (MaR1) contents in type 2 diabetic patients with or without diabetic foot ulcer and to analyze the association of MaR1 concentrations with several metabolism-related parameters. Methods. Plasma MaR1 concentrations were analyzed in 96 subjects with normal glucose tolerant (NC, ), type 2 diabetes (T2DM, ), or diabetic foot ulcer (DFU, ). The intravenous glucose tolerance test (IVGTT) and biochemical parameters were measured in all participants. Results. Plasma MaR1 concentrations were significant decreased in type 2 diabetes patient with or without DFU compared with NC (both ) and were lowest in DFU patients among these 3 groups. (DFU vs. T2DM, ). Plasma MaR1 concentrations were negatively correlated with BMI, waist circumference (Wc), waist hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), LDL-c, FPG, 2hPG, HbA1c, and 新疆11选5走势图ostasis model assessment for insulin resistance (HOMA-IR) (all ) and were positively correlated with HDL-c, acute insulin response (AIR), area under the curve of the first-phase (0-10 min) insulin secretion (AUC), and 新疆11选5走势图ostasis model assessment for beta-cell function (HOMA-β) (all ). After adjusting for age and sex, Wc, WHR, TG, FPG, 2hPG, HbA1c, HOMA-IR, AIR, AUC, and HOMA-β remain statistically significant (all ). Conclusions. Plasma MaR1 concentration were decreased in T2DM with or without DFUs and were the lowest in DFU patients. The decreased plasma MaR1 strongly associated with obesity, impaired glucose and lipid metabolism, reduced first-phase of glucose-stimulated insulin secretion, and enhanced insulin resistance.
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