Corrigendum: PHLDA1 Suppresses TLR4-Triggered Proinflammatory Cytokine Production by Interaction With Tollip.

[This corrects the article DOI: 10.3389/fimmu.2022.731500.].

PHLDA1 Suppresses TLR4-Triggered Proinflammatory Cytokine Production by Interaction With Tollip.

Pleckstrin homology-like domain, family A, member 1 (PHLDA1) has been reported to be expressed in many mammalian tissues and cells. However, the functions and exact mechanisms of PHLDA1 remain unclear. In this study, we found that PHLDA1 expression was significantly altered in macrophages after exposure to lipopolysaccharide (LPS) in vitro, suggesting that PHLDA1 may be involved in the regulation of TLR4 signaling pathway activated by LPS. PHLDA1 attenuated the production of LPS-stimulated proinflammatory cytokines (TNF-α, IL-6, and IL-1ß). Further research showed that the phosphorylation levels of some important signal molecules in TLR4/MyD88-mediated MAPK and NF-κB signaling pathways were reduced by PHLDA1, which in turn impaired the transcription factors NF-κB and AP1 nuclear translocation and their responsive element activities. Furthermore, we found that PHLDA1 repressed LPS-induced proinflammatory cytokine production via binding to Tollip which restrained TLR4 signaling pathway. A mouse model of endotoxemia was established to confirm the above similar results. In brief, our findings demonstrate that PHLDA1 is a negative regulator of LPS-induced proinflammatory cytokine production by Tollip, suggesting that PHLDA1 plays an anti-inflammatory role through inhibiting the TLR4/MyD88 signaling pathway with the help of Tollip. PHLDA1 may be a novel therapeutic target in treating endotoxemia.

Arginine methylation by PRMT2 promotes IFN-ß production through TLR4/IRF3 signaling pathway.

A balance between the positive and negative regulation of toll-like receptor (TLR) signaling pathways is required to avoid detrimental and inappropriate inflammatory responses. Although some protein post-translational modifications (PTMs) such as phosphorylation and ubiquitination have been demonstrated to potently modulate innate immune responses, the role of methylation, an important PTM, control of TLR4 signaling pathway remains unclear. In this study, we found that protein arginine methyltransferase 1, 2 and 3 (PRMT1, 2 and 3) were recruited to methylate TLR4-CD (cytoplasmic domain) after lipopolysaccharide (LPS) stimulation respectively, but the effect of PRMT2 on arginine methylation of TLR4-CD is the most significant among above three PRMTs, which prompted us to focus on PRMT2. Reduction of PRMT2 expression down-regulated arginine (R) methylation level of TLR4 with or without LPS treatment. Methionine 115 (M115) mediated PRMT2 catalyzed-arginine methylation of TLR4 on R731 and R812. Furthermore, PRMT1, 2 and 3 was recruited to methylate interferon regulatory factor 3 (IRF3) after LPS stimulation respectively, but the effect of PRMT2 on arginine methylation of IRF3 is the most significant among the above three PRMTs. Arginine methylation of TLR4 on R812 or arginine methylation of IRF3 on R285 mediated the interaction between TLR4 and IRF3 respectively. Arginine methylation of IRF3 on R285 induced by LPS led to its dimerization and promoted its translocation from the cytoplasm to the nucleus. In addition, the enhancement of arginine methylation of TLR4 induced by PRMT1 or 2 increased IRF3 transcription activity with or without LPS treatment, while PRMT2 with histidine 112 glutamine (H112Q) or methionine 115 isoleucine (M115I) mutation and TLR4 with arginine 812 lysine (R812K) mutation decreased it. Arginine methylation of TLR4 on R812 or PRMT2 enhanced interferon-ß (IFN-ß) production. Our study reveals a critical role for PRMT2 and protein arginine methylation in the enhancement of IFN-ß production via TLR4/IRF3 signaling pathway and may provide a therapeutic strategy to control endotoxemia.

Current insights into the expression and functions of tumor-derived immunoglobulins.

Numerous studies have reported expressions of immunoglobulins (Igs) in many human tumor tissues and cells. Tumor-derived Igs have displayed multiple significant functions which are different from classical Igs produced by B lymphocytes and plasma cells. This review will concentrate on major progress in expressions, functions, and mechanisms of tumor-derived Igs, similarities and differences between tumor-derived Igs and B-cell-derived Igs. We also discuss the future research directions of tumor-derived Igs, including their structural characteristics, physicochemical properties, mechanisms for rearrangement and expression regulation, signaling pathways involved, and clinical applications.

[Study on incompatibility of traditional Chinese medicines].

The incompatibility of traditional Chinese medicines is related to the clinical medication safety, so has attracted wide attentions from the public. With the deepening of studies on the incompatibility of traditional Chinese medicines represented by 18 incompatible herbs, the incompatibility of theory traditional Chinese medicines has raised to new heights. From the origin of incompatibility theory of traditional Chinese medicines, relationship of herbs, harms of incompatible herbs and principle of prevention to toxic effects of specific incompatible medicines, the innovation and development of the traditional Chinese medicine incompatibility theory was explored. Structurally, the incompatibility of traditional Chinese medicines refers to the opposition of two herbs based on seven emotions and clinical experience. The combination of incompatible herbs may lead to human harms, especially latent harm and inefficacy of intervention medicines. The avoidance of the combination of incompatible herbs and the consideration of both symptoms and drug efficacy are the basic method to prevent adverse reactions. The recent studies have revealed five characteristics of incompatible herbs. Toxicity potentiation, toxication, efficacy reduction and inefficacy are the four manifestations of the incompatible relations. The material changes can reflect the effects of toxicity potentiation and toxication of opposite herbs. The accumulation of toxicity and metabolic changes are the basis for latent harms. The antagonistic effect of main efficacies and the coexistence of positive and negative effects are the distinctive part of the incompatibility. The connotation of incompatible herbs plays an important role in the innovation of the traditional Chinese medicine incompatibility theory.

[Exploration on eighteen incompatible medicaments of chest pain prescriptions based on association rules mining].

OBJECTIVE: To investigate the laws of eighteen incompatible medicaments of the chest pain prescriptions based on association rules mining. METHOD: The database of chest pain prescription was established and then the chest pain prescriptions composed of eighteen incompatible medicaments were screened. The dynasty, couplet medicines, the property and flavor of drugs and preparation form were analyzed with the frequent item sets and corresponding analysis methods. RESULT: Eight hundred and fifty chest pain prescriptions were collected, and 88 of them contained eighteen incompatible medicaments, taking 10.3% of all; the applications of ancient and modern chest pain prescriptions containing eighteen incompatible medicaments are significant difference (P < 0.05). Ancient formulas, mainly focus on the eastern jin dynasty and tang dynasty, are more often used than the modern formulas. The most common anti-drugs is on the Fuzi-Pinellia, Chuanwu-Pinellia; the property and flavor of drugs is bitter cold most closely; the decoction of the formulas is mostly used. CONCLUSION: Eighteen incompatible medicaments account for about ten percent of the chest pain prescription, not an uncommon side. There are certain rules for application of anti-drug compatibility to treat chest pain.

[Progress in research on function and mechanism of cardiac vascular system of taurine].

The function for cardiac vascular system of taurine is extensive, and the mechanism is complicated. Taurine protects the cells from the cell injury caused by ischemia etc. Through repressing apoptosis, prevents endothelial dysfunction caused by hyperglycemia, hypercholesterolemia, smoking and homocysteine; suppresses the proliferation and calcification in vascular smooth muscle cells, promotes metabolization and excretion of cholesterol in the animal models of hyperlipemia, and confers the resistance to an oxidant, hypochlorous acid, produced by neutrophil on cells, and taurine chrolamine to inhibit activation of NF-kappaB, which might be associated with anti-atherosclerotic effect. Taurine mainly acts inside the cell. However, taurine transport system becomes aberrant in pathological myocardial and vascular tissue. In addition, taurine improves cardiovascular function in fructose-induced hypertension and an iron-overload murine animal models.