Molecular Characterization of Pro-Inflammatory Cytokines Interleukin-1β and Interleukin-8 in Asian Elephant (Elephas maximus)

Interleukin (IL)-1β and IL-8 are pro-inflammatory cytokines produced primarily by monocytes and macrophages in response to a variety of microbial and nonmicrobial agents. As yet, no molecular data have been reported for IL-1β and IL-8 of the Asian elephant. In the present study, we have cloned and sequenced the cDNA encoding IL-1β and IL-8 of the Asian elephant. The open reading frame (ORF) of Asian elephant IL-1β is 789 bp in length, encoded a propeptide of 263 amino acid polypeptide. The predicted protein revealed the presence of IL-1 family signature motif and an ICE cut site. Whereas, IL-8 contained 321 bp of open reading frame. Interestingly, the predicted protein sequence of 106 aa, contains an ELR motif immediately upstream of the CQC residues, common in all vertebrate IL-8 molecules. Identity levels of the nucleic acid and deduced amino acid sequences of Asian elephant IL-1β ranged from 68.48 (Squirrel monkey) to 98.57% (African elephant), and 57.78 (Sheep) to 98.47% (African elephant), respectively, whereas that of IL-8 ranged from 72.9% (Human) to 87.8% (African elephant), and 63.2 (human, gorilla, chimpanzee) to 74.5% (African elephant, buffalo), respectively. The phylogenetic analysis based on deduced amino acid sequenced showed that the Asian elephant IL-1β and IL-8 were most closely related to African elephant. Molecular characterization of these two cytokines, IL-1β and IL-8, in Asian elephant provides fundamental information necessary to progress the study of functional immune responses in this animal and gives the potential to use them to manipulate the immune response as recombinant proteins.     

干扰素刺激基因表达对Peg-IFN抗乙型肝炎病毒免疫应答的影响

为了揭示干扰素刺激基因(interferon-stimulated gene, ISG)表达的改变对乙型肝炎病毒感染治疗效果的影响,本研究检测了干扰素刺激基因STAT1、MX和SOCS3在慢性乙型肝炎患者的外周血单核细胞(peripheral blood mononuclear cell, PBMC)和肝脏样品中的表达情况。结果显示,采用聚乙二醇干扰素(Peg-IFN)治疗后,Peg-IFN应答者的PBMC和肝组织中的STAT1和MX表达水平显著升高,而非应答者的SOCS3表达显著升高。在应答者的活组织检查中,Peg-IFN治疗24 h后细胞核中磷酸化STAT1的染色比例显著增加,而非应答者在治疗前肝细胞核染色比例较高,治疗后染色比例显著减少。此外,治疗前非应答者的肝SOCS3表达水平显著高于应答者,并且随着IFN的治疗SOCS3表达继续增加。本研究表明,STAT1和MX是Peg-IFN抗病毒免疫应答的正向调节因子,而SOCS3 (JAK/STAT途径的负调节因子)激活干扰素刺激基因的负调控,并抑制Peg-IFN的免疫应答。     

Nonparametric Analysis of Thermal Proteome Profiles Reveals Novel Drug-binding Proteins*

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Highlights

• •Method for the analysis of response curves from thermal proteome profiling (TPP).
• •NPARC uses nonparametric statistics and provides false discovery-rate (FDR) control.
• •Increased proteome coverage and sensitivity to identify drug-binding proteins.

     

Effects of low-level combined static and weak low-frequency alternating magnetic fields on cytokine production and tumor development in mice

We investigated the effects of weak combined magnetic fields (MFs) produced by superimposing a constant MF (in the range 30 - 150 µT) and an alternating MF (100 or 200 nT) on cytokine production in healthy Balb/C male mice exposed 2 h daily for 14 days. The alternating magnetic field was a sum of several frequencies (ranging from 2.5 - 17.5 Hz). The frequencies of the alternating magnetic field were calculated formally based on the cyclotron resonance of ions of free amino acids (glutamic and aspartic acids, arginine, lysine, histidine, and tyrosine). The selection of different intensity and frequency combinations of constant and alternating magnetic fields was performed to find the optimal characteristics for cytokine production stimulation in immune cells. MF with a constant component of 60 μT and an alternating component of 100 nT, which was a sum of six frequencies (from 5 to 7 Hz), was found to stimulate the production of tumor necrosis factor-α, interferon-gamma, interleukin-2, and interleukin-3 in healthy mouse cells and induce cytokine accumulation in blood plasma. Then, we studied the effect of this MF on tumor-bearing mice with solid tumors induced by Ehrlich ascite carcinoma cells by observing tumor development processes, including tumor size, mouse survival rate, and average lifespan. Tumor-bearing mice exposed to a combined constant magnetic field of 60 μT and an alternating magnetic field of 100 nT containing six frequencies showed a strong suppression of tumor growth with an increase in survival rate and enhancement of average lifespan.     

肿瘤治疗中细胞因子递送策略的研究进展

细胞因子多数是由机体免疫细胞和某些非免疫细胞产生的,对细胞的生长、增殖、分化均有调节作用的一类具有生物活性的蛋白质。在肿瘤治疗中,细胞因子作为一种蛋白质药物,具有体内半衰期短、全身毒副作用大等特点,因而选择细胞因子递送策略时需考虑以上因素。文章简要介绍了几种常见的细胞因子,并综述了近年来在肿瘤治疗中细胞因子递送策略的研究进展。     

Cell-Type-Specific Gene Expression Profiling in Adult Mouse Brain Reveals Normal and Disease-State Signatures

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Erythrocyte immune system: beyond the gas transporter

Accumulating research has revealed that erythrocytes play unique roles in the innate immune system. Once thought of as immunologically inert cells, erythrocytes are functional cells that exert diverse immunological effects. Although mature mammal erythrocytes lack internal organelles, they express various receptors, which provide an extraordinary ability for erythrocytes to clear or sequester circulating molecules that affect immune functions. In this review, we elucidate some crucial immunological molecules associated with erythrocytes, such as CR1, CD47, TLR9, and cytokines. CR1 acts as a bridge in clearing off immune complexes and an entrance gate for some pathogens. CD47, once bound to SIRPα, generates an inhibitory signal in macrophage phagocytosis. Reciprocally, erythrocyte CD47 undergoes a conformational change during oxidative stress-induced cellular senescence, subsequently activating phagocytic signals through binding to TSP-1. TLR9 recognizes unmethylated CpG-DNA present in viruses and bacteria. Erythrocyte TLR9 also binds to and eliminates mitochondrial DNA. Erythrocytes can recruit chemokines and modulate plasma chemokine levels through the Duffy antigen receptor for chemokines (DARC). Moreover, erythrocytes may exert immune functions by releasing danger-associated molecular patterns (DAMPs), i.e., heme, IL-33, ATP, and Hsp70. Heme bound with toll-like receptor 4 (TLR4) has the potential to trigger an inflammatory response. Similarly, IL-33, ATP, and Hsp70 from damaged erythrocytes may be involved in the innate immune response via diverse signaling mechanisms. This review provides novel insight into the immunological functions of erythrocytes, which play an irreplaceable role in innate immune responses. We argue that erythrocyte-involved immune function is a widespread area warranting intensive investigation.