1.Biologics for targeting inflammatory cytokines and their clinical application.
Jin CHEN ; Mian XIE ; Lujun LI ; Dongxu LIU ; Mengyuan LIU
Chinese Journal of Biotechnology 2019;35(6):1009-1020
Inflammatory cytokines can mediate many biological processes and are tightly regulated by the body. Loss of control can trigger a range of diseases such as autoimmune inflammation and cancer. Therefore, a number of biological agents that can effectively regulate the biological effects of inflammatory cytokines such as recombinant anti-inflammatory cytokines, cytokine receptors and neutralizing antibodies have been extensively used in the treatment of related diseases caused by the imbalance of inflammatory cytokines. In recent years, in particular, a number of new innovative biological agents for blocking and regulating cytokine activities are emerging. In this article, we review the recent development and clinical use of the biologics targeting TNF-α, IL-1, IL-6 and IL-17, and point out their inherent limitations and clinical risks. Finally, based on the research findings of our own and other scholars, we suggest some approaches and methods for reducing their side-effects and clinical risk. We consider that using modern biotechnology to improve the tissue specificity to inflammatory site and tumor will be an important development direction of such biologics.
Biological Products
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metabolism
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Cytokines
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Humans
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Inflammation
2.Chronic prostatitis and cytokines.
National Journal of Andrology 2011;17(10):939-942
Chronic prostatitis (CP) is a common disease in men, and its pathogenesis remains to be clarified. The precise regulation of cytokines is involved in all types and all stages of CP. The interaction of inflammation, inflammatory cells and cytokines leads to the development and progression of CP. With further understanding of the immunological and molecular biological mechanisms of the disease and more inflammatory cytokines used in its detection, it is of special significance to apply cytokines in the classification and treatment of CP. This review outlines the roles of cytokines in the pathogenesis of CP, particularly chronic pelvic pain syndrome (CPPS), their relationship with CP, and their significance in the classification and diagnosis of CP/CPPS.
Chronic Disease
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Cytokines
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metabolism
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Humans
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Male
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Prostatitis
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etiology
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metabolism
3.The potential of avian cytokines as immunotherapeutics and vaccine adjuvants.
Chinese Journal of Biotechnology 2003;19(2):141-146
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
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metabolism
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Animals
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Cytokines
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genetics
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immunology
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metabolism
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Immunotherapy
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methods
4.Relationship between the resuscitation promoting role of resuscitation promoting factor and the initial bacteria amount of dormant Mycobacterium tuberculosis.
Zhong-Quan LIU ; Ai-Ying XING ; Shu-Xiang GU ; Hong-Yan JIA ; Zong-De ZHANG
Acta Academiae Medicinae Sinicae 2009;31(4):423-426
OBJECTIVETo investigate the relationship between the resuscitation promoting role of resuscitation promoting factor and the initial bacteria amount of dormant Mycobacterium tuberculosis.
METHODSMycobacterium tuberculosis (dormant bacteria) was cultured for 100 days, then diluted into 1 mg/ml concentration with 7H9, and further diluted into 0.5, 0.25, 0.125, 0.0625, and 0.03125 mg/ml. Twelve new tubes added with 5 ml 7H9 and divided into two groups: the first group was added with the resuscitation-promoting factor protein, and the second group as control was added with 7H9. In each group the above diluted solutions were added. The tubes were located at 37 degrees C for culture. Optical density (OD) was detected on day 15, 25, 30, and 35. From each tube 1 microl culture solution was plated on 7H11 medium for colony counting.
RESULTSOD detection showed that bacteria proliferation in each group had positive linear correlation (P < 0.05, P < 0.01), indicating that the resuscitation-promoting factor played a similiar role in solutions with different dilution concentrations. 7H11 results and the OD results show that these two detection methods in each group had linear correlation (P < 0.05, P < 0.01), indicating that these two methods showed consistent test results.
CONCLUSIONThe resuscitation-promoting factor has no effect on the resuscitation of dormant Mycobacterium tuberculosis and its initial bacteria amount.
Bacterial Proteins ; metabolism ; Cytokines ; metabolism ; Mycobacterium tuberculosis ; physiology ; Resuscitation
5.Effects of the 24 N-terminal amino acids of p55PIK on endotoxinstimulated release of inflammatory cytokines by HaCaT cells.
Feng LV ; Wei YOU ; Yang YU ; Jun-bo HU ; Bin ZHANG ; Jing WANG
Journal of Huazhong University of Science and Technology (Medical Sciences) 2013;33(4):587-593
This study aimed to examine the effect of the 24 N-terminal amino acids (N24) of p55PIK, a regulatory subunit of phosphatidylinositol 3-kinase (PI3K), on the endotoxin lipopolysaccharide (LPS)-stimulated release of the cytokines (CKs) by HaCaT cells. The fusion protein, trans-acting activator of transcription (TAT)-N24 (an experimental peptide, EP) containing the N24 of PI3K-p55PIK, was constructed, and TAT-N24 fusion peptide was expressed and identified in BL21 E·coli. HaCaT cells (a human keratinocyte cell line) was cultured and stimulated by LPS at 100 ng/mL for 1, 2, 4, 8, 16 or 24 h, or by LPS at 10, 100 ng/mL, 1, 10 or 100 μg/mL of for 4 h. Changes in the protein and mRNA levels of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8) released by HaCaT cells following EP intervention were determined by enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (PCR). Immunofluorescence confocal laser scanning microscopy was utilized to detect the protein expression and translocation of the p65 subunit of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB p65) in HaCaT cells. The expression of the NF-κB inhibitor alpha (IκB-α) protein in LPS-stimulated HaCaT cells after the EP intervention was measured by Western blotting. The results showed that EP treatment increased TNF-α secretion from HaCaT cells. EP at certain concentrations could effectively inhibit the LPS-stimulated release of TNF-α, IL-6 and IL-8 from HaCaT cells. The ELISA assay demonstrated that the concentrations of TNF-α, IL-6 and IL-8 in the supernatants of LPS-stimulated cells were reduced from 208.06±30.18, 86.4±9.78 and 260.59±54.05 pg/mL to 121.78±22.26, 53.18±7.36 and 125.08±35.17 pg/mL, respectively, in the supernatants of cells treated by LPS and EP combined. Real-time PCR also revealed that the expression of the three pro-inflammatory CKs was significantly decreased after EP intervention. Immunofluorescence confocal laser scanning microscopy showed that NF-κB p65 protein was primarily expressed in the cytoplasm of non-stimulated HaCaT cells. After LPS stimulation, NF-κB p65 was translocated into the nucleus, and the nuclear expression of this protein increased. The nuclear NF-κB p65 protein expression was inhibited after the addition of EP. Western blotting showed that IκB-α expression began to decrease 30 min after LPS stimulation and declined to a trough 4 h later. IκB-α expression began to gradually recover 16 h after LPS stimulation but remained at a lower-than-normal level at 24 h. Greater IκB-α expression was found in cells treated with LPS and EP combined than those treated with LPS alone. It was concluded that EP can effectively inhibit the LPS-stimulated expression of TNF-α, IL-6, and IL-8, which involves the inhibition of the hydrolysis of IκB-α and thereby blockage of the nuclear translocation of NF-κB p65.
Amino Acids
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metabolism
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Cell Line
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Cytokines
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metabolism
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Endotoxins
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metabolism
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Humans
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Inflammation
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metabolism
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Phosphatidylinositol 3-Kinases
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metabolism
6.The effects of cold exposure on the ileum mechanical barrier in mice and its mechanisms.
Meng-Meng LIU ; Yan ZHANG ; Zi-Wei ZHANG ; Jian-Bin YUAN ; Jing-Ru GUO
Chinese Journal of Applied Physiology 2022;38(3):279-283
Objective: To study the mechanisms of cold exposure mediated ileum mechanical barrier injury in mice. Methods: Twenty mice were randomly divided into the control and cold exposure groups. Both the control and cold exposure groups were placed in the climate room with (24±2)℃ and 40% humidity. The mice in the cold exposure group were moved to the climate room at (4±2)℃ every day for 3 hours for three consecutive weeks. Three weeks later, the ileum tissues of mice were collected. Changes in ileum tissue structure were observed by hematoxylin-eosin staining and Masson staining. The related protein expression levels of the tight junction, inflammatory cytokines, and the NF-κB pathway were detected by Western blot. Results: Compared with the control group, the circular muscle layer of the ileum in cold exposed mice became thin, a large number of inflammatory cells infiltrated, the length of villi became short, the depth of recess was increased, and tissue fibrosis appeared. The expression levels of ideal tight junction-associated proteins in cold exposed mice were decreased significantly (P<0.05), while the protein expression levels of IL-1β, IL-6 and phosphorescent p65 were increased significantly (P<0.05). Conclusion: Cold exposure can damage the tight junction of the mouse ileum, destroy the integrity of the mechanical barrier and activate the NF-κB signaling pathway to promote the occurrence of the inflammatory response.
Animals
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Cytokines/metabolism*
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Ileum/metabolism*
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Intestinal Mucosa
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Mice
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NF-kappa B/metabolism*
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Tight Junctions/metabolism*
7.House dust mite disrupts the airway epithelial barrier by affecting the expression of thymic stromal lymphopoietin through inducing Atg5.
Zicong ZHOU ; Shixiu LIANG ; Zili ZHOU ; Jieyi LIU ; Xiaojing MENG ; Laiyu LIU ; Fei ZOU ; Changhui YU ; Shaoxi CAI
Chinese Medical Journal 2023;136(17):2128-2130
8.Regulation of the Collagen Gene Expression.
Korean Journal of Dermatology 1995;33(6):1005-1013
The genes that codify the subunits of the fibril-forming collagen constitute an evolutionarily related group within the collagen multigene family, Deposition of fibrillar molecules in the extrcellular matrix of several tissues influences a number of cellular activities such as adhesion, proliferation, and migration. In the developing and adult organisms, temporal and spatial expression of collasgen genes is modulated by a variety of cytokines and hormones, Likewise, transcription of collagen genes in tissue cultures can be greatly affected by the action of these substances and by chemical or viral transformation as well. Cytokine-mediated increase of collagen deposition on response to environmental stimuli is also the major histopathological feature of clinically distinct that similarly lead to overt firrotic processes. It is my heartily with to elucidate the mechanisms that regulate tissue specific expression of the human collagen genes a prerequisite for understanding the pathophysiology of diseased processes. Involving collagen metabolism, such as scleroderma.
Adult
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Collagen*
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Cytokines
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Gene Expression*
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Humans
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Metabolism
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Multigene Family
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Psoriasis