With the imminent and widespread ban of the use of antibiotic feed additives and chemical antimicrobials in food production animals, alternative measures need to be sought to ensure that the livestock industry will not be adversely affected. Cytokines are proteins that control the type and extent of an immune response following infection or vaccination. They therefore represent excellent naturally occurring therapeutics. The identification, cloning and characterisation of cytokine genes in chickens have lagged somewhat behind similar work in mammals. Progress in isolating chicken homologues of mammalian cytokines has also been slowed by the generally low level of sequence similarity. Chicken cytokine genes that have been cloned to date include ChIFN-gamma, ChIL-1beta, ChIFN-alpha, ChIL-15, ChIL-18, ChIL-8, ChIL-2, ChIL-6, ChIL-16, SCF, MGF, TGFbeta, Lymphotactin, MIP-1beta, CXC and CC chemokines, so the use of cytokines in poultry has become more feasible with the discovery of a number of avian cytokine genes. The delivery methods for chicken cytokine are of prime importance and are required to be safe, easy to administer and cost-effective. Live viral vectors such as fowl adenovirus (FAV) expressing cytokine genes can be delivered via drinking water or aerosol sprays, making it very easy to administer. Since the immune system of chickens is similar to that of mammals, they offer an attractive model system to study the effectiveness of cytokine therapy in the control of disease in livestock. This review focus on the recent advances made in avian cytokines, with a particular focus on their assessment as therapeutic agents and vaccine adjuvants.
Adjuvants, Immunologic ; metabolism ; Animals ; Cytokines ; genetics ; immunology ; metabolism ; Immunotherapy ; methods

The developmental program of T helper and regulatory T cell lineage commitment is governed by both genetic and epigenetic mechanisms. The principal events, signaling pathways and the lineage determining factors involved have been extensively studied in the past ten years. Recent studies have elucidated the important role of chromatin remodeling and epigenetic changes for proper regulation of gene expression of lineage-specific cytokines. These include DNA methylation and histone modifications in epigenomic reprogramming during T helper cell development and effector T cell functions. This review discusses the basic epigenetic mechanisms and the role of transcription factors for the differential cytokine gene regulation in the T helper lymphocyte subsets.
Animals ; Cytokines/metabolism ; Epigenesis, Genetic/*genetics ; Gene Expression Regulation/genetics/physiology ; Humans ; T-Lymphocytes/*metabolism

OBJECTIVETo explore the mechanism of natural moxibustion on regulating immune imbalance in asthma rats.

METHODSSeventy SD male rats were divided into a normal group, a placebo group, a dexamethasone group, a big-cake for long-course moxibustion group, a big-cake for short-course moxibustion group, a small-cake for long-course moxibustion group and a small-cake for short-course moxibustion group, ten rats in each one. The rat model of asthma was established by egg albumen sensitization and stimulation in all the groups except the normal group. The natural moxibustion was used in all moxibustion groups, in which big cake of 1 cmX 1 cm size was used in the big-cake groups and small cake of 0.5 cmX 0. 5 cm size was used in the small cake groups. According to relevant acupoints, the natural moxibustion was performed, 5 h per time, once a day. Four times of treatment was considered one course, and three courses were required in the long-course groups and one course was required in the short-course groups. Intraperitoneal injection of dexamethasone was applied in the dexamethasone group, which had the same course as long-course moxibustion group. After the treatment, changes of EOS in peripheral blood of asthma rats were observed; enzyme linked immunosorbent assay (ELISA) was applied to test the contents of IgE, IL-4 and IFN-gamma in the lung tissue; real-time Q-PCR method was adopted to measure the expression level of transcription factor T-bet and GATA binding protein 3 (GATA-3) in the lung tissue.

RESULTSCompared with the normal group, the EOS in whole blood as well as IL-4 and IgE in plasma were all increased in the placebo group (all P< 0. 01), IFN-gamma in plasma was obviously decreased (P<0. 01); while the levels of EOS, IgE and IL-4 were significantly reduced (all P<0. 01), the content of IFN-gamma was increased (P<0. 01) in all moxibustion groups and dexametnasone group. Compared with the normal group, the expression of T-bet mRNA in the placebo group was significantly reduced (P<0. 01). Each treatment group could significantly increase the expression of T-bet mRNA and reduce that of GATA-3 mRNA (P<0. 01). Compared with the short-course moxibustion groups, the expression of T-bet mRNA was obviously increased in the long-course moxibustion group and dexamethasone group (both P<0.01), and that of GATA-3 mRNA was reduced (P<0.01). There was no significant difference between long-course moxibustion group and dexamethasone group (P> 0. 05), and also no significant difference could be seen between big-cake moxibustion group and small-cake moxibustion group (P>0. 05).

CONCLUSIONThe natural moxibustion could obviously reduce airway inflammation in asthma rats. With time passing, the efficacy is enhanced, indicating evident timeliness, which has no apparent relationship with the size of moxibustion cake.

Animals ; Asthma ; genetics ; metabolism ; therapy ; Cytokines ; genetics ; metabolism ; Humans ; Male ; Moxibustion ; Rats ; Rats, Sprague-Dawley ; Transcription Factors ; genetics ; metabolism

To investigate whether HIV-1 infection affects expression of interferon-stimulated gene 15 (ISG15) and determine the antiviral effect of ISG15 in vitro, ISG15 expression at transcription and protein level and supernatant p24 of HIV-1 was detected in various HIV-1 infected or transfected cell lines, respec tively. HIV-1 molecular clone pNL4-3 was used to transfect 293T, TZM-bl and HeLa cells while HIV-1 pseudo-typed virus was used to infect Jurkat, MT-1 and THP-1 cells. After twenty-four hours post infection or transfection, cells were harvested for extraction of total RNAs and subsequently used in real time PCR for quantification of ISG15 transcriptional expression. After forty-eight hours post infection or transfection, cells were harvested for extraction of total proteins to detect ISG15 protein expression. A significant up-regulation of ISG15 at transcription level was observed in HIV-1 infected or transfected cell lines, particulaly in THP-1 and TZM-bl cells. Up-regulation of ISG15 protein was observed only in TZM-bl cell. Cotransfection of ISG15 and HIV-1 indicated that ISG15 inhibited production of HIV-1 progeny virus in a dose and time depend manner in 293T cell but not TZM-bl cell. These results revealed upregulating ISG15 expression in transcriptional level and potential antagonistic mechanism against ISG15 by HIV-1 infection, simultanelusly.
Base Sequence ; Cell Line ; Cytokines ; genetics ; metabolism ; HIV Infections ; genetics ; metabolism ; virology ; HIV-1 ; physiology ; Humans ; Interferons ; metabolism ; Molecular Sequence Data ; Ubiquitins ; genetics ; metabolism ; Up-Regulation

Cytokines ; genetics ; metabolism ; Endotoxins ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Gene Expression ; Humans ; Liver Diseases, Alcoholic ; genetics ; metabolism ; RNA, Messenger ; genetics ; metabolism ; Reverse Transcriptase Polymerase Chain Reaction

This paper aims to explore the effects of chicken interferon-γ (ChIFN-γ) and interleukin-2 (ChIL-2) on type 1 helper (Th1) T lymphocyte differentiation. To be specific, ChIFN-γ and ChIL-2 were first expressed in Escherichia coli competent cells and then purified by Ni-NTA affinity chromatography. Different concentration of ChIFN-γ and ChIL-2 were employed to stimulate the lymphocytes in chicken peripheral blood which had been activated by concanavalin A (Con A), and the mRNA levels of cytokines related to Th1 cell differentiation were detected by real-time quantitative PCR (RT-qPCR). The results showed that both ChIFN-γ and ChIL-2 can significantly up-regulate mRNA levels of cytokines related to Th1 cell differentiation and the optimal concentration was 12.5 μg/mL and 25.0 μg/mL, respectively. In addition, specific-pathogen-free (SPF) chickens were immunized with ChIL-2 or ChIFN-γ together with H9N2 vaccine, or H9N2 vaccine alone by oral administration or intramuscular injection, respectively. The mRNA levels of cytokines related to Th1 cell differentiation were detected after immunization. The results showed that ChIFN-γ and ChIL-2 significantly up-regulated the mRNA levels of cytokines related to Th1 cell differentiation induced by H9N2 vaccine compared with H9N2 vaccine alone, and that the intramuscular injection was better than oral administration. In this study, we verified that ChIFN-γ and ChIL-2 can significantly enhance mRNA levels of cytokines related to Th1 cell differentiation induced by ConA or H9N2 vaccine in vitro and in vivo. The results of this study can lay a theoretical basis for using ChIFN-γ and ChIL-2 as vaccine adjuvants.
Animals ; Cell Differentiation ; Chickens ; Concanavalin A ; Cytokines/genetics* ; Influenza A Virus, H9N2 Subtype/genetics* ; Interferon-gamma/metabolism* ; Interleukin-2/genetics* ; RNA, Messenger

Aged ; Bone Marrow ; metabolism ; Cytokines ; metabolism ; Female ; Humans ; Karyotype ; Male ; Mesenchymal Stromal Cells ; Middle Aged ; Myelodysplastic Syndromes ; genetics ; metabolism

OBJECTIVE: To investigate the inflammatory effects of Cinobufotalin on monocytes in resting state and macrophages in activated state and its molecular mechanism. METHODS: THP-1 cells were stimulated with Phorbol 12-myristate 13-acetate to induce differentiation into macrophages. Lipopolysaccharides was added to activate macrophages in order to establish macrophage activation model. Cinobufotalin was added to the inflammatory cell model for 24 h as a treatment. CCK-8 was used to detect cell proliferation, Annexin V /PI double staining flow cytometry was used to detect cell apoptosis, flow cytometry was used to detect macrophage activation, and cytometric bead array was used to detect cytokines. Transcriptome sequencing was used to explore the gene expression profile regulated by Cinobufotalin. Changes in the significantly regulated molecules were verified by real-time quantitative polymerase chain reaction and Western blot. RESULTS: 1∶25 concentration of Cinobufotalin significantly inhibited the proliferation of resting monocytes(P<0.01), and induced apoptosis(P<0.01), especially the activated macrophages(P<0.001, P<0.001). Cinobufotalin significantly inhibited the activation of macrophages, and significantly down-regulated the inflammatory cytokines(IL-6, TNF-α, IL-1β, IL-8) released by activated macrophages(P＜0.001). Its mechanism was achieved by inhibiting TLR4/MYD88/P-IκBa signaling pathway. CONCLUSION Cinobufotalin can inhibit the inflammatory factors produced by the over-activation of macrophages through TLR4/MYD88/P-IκBa pathway, which is expected to be applied to the treatment and research of diseases related to the over-release of inflammatory factors.
Humans ; Toll-Like Receptor 4/metabolism* ; Myeloid Differentiation Factor 88/genetics* ; Macrophages/metabolism* ; Cytokines/metabolism* ; Lipopolysaccharides/pharmacology* ; NF-kappa B

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease caused by inflammatory cells. Various inflammatory cells involved in RA include fibroblast-like synoviocytes, macrophages, CD4⁺T-lymphocytes, B lymphocytes, osteoclasts and chondrocytes. The close interaction between various inflammatory cells leads to imbalance of immune response and disorder of the expression of mRNA in inflammatory cells. It helps to drive production of pro-inflammatory cytokines and stimulate specific antigen-specific T- and B-lymphocytes to produce autoantibodies which is an important pathogenic factor for RA. Competing endogenous RNA (ceRNA) can regulate the expression of mRNA by competitively binding to miRNA. The related ceRNA network is a new regulatory mechanism for RNA interaction. It has been found to be involved in the regulation of abnormal biological processes such as proliferation, apoptosis, invasion and release of inflammatory factors of RA inflammatory cells. Understanding the ceRNA network in 6 kinds of RA common inflammatory cells provides a new idea for further elucidating the pathogenesis of RA, and provides a theoretical basis for the discovery of new biomarkers and effective therapeutic targets.
Humans ; Arthritis, Rheumatoid/genetics* ; MicroRNAs/metabolism* ; Synoviocytes/pathology* ; Cytokines/metabolism* ; RNA, Messenger/metabolism* ; Fibroblasts/pathology* ; Cell Proliferation

Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family which plays roles in the nucleus as a nuclear factor and is released by damaged or necrotic cells to act as a cytokine. It can be released via damaged or necrotic cells and functions as a cytokine. The released IL-33 activates the downstream NF-κB and MAPKs signaling pathways through the isomers of the specific receptor ST2 and the interleukin-1 receptor accessory protein (IL-1RAcP), resulting in danger signals and the activated multiple immune responses. IL-33 is abnormally expressed in various tumors and involves in tumorigenesis, development, and metastasis. Moreover, IL-33 can play both pro-tumor and anti-tumor roles in the same type of tumor.
Cytokines ; Humans ; Interleukin-33/genetics* ; MAP Kinase Signaling System ; NF-kappa B/metabolism* ; Neoplasms