• Title/Summary/Keyword: Innate Immunity

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Pharmaco-medical Application of Antimicrobial Peptides Derived from Insect (곤충유래 항균 펩티드의 의약학적 적용)

  • Lee, Joon Ha;Kim, In-Woo;Kim, Mi-Ae;Yun, Eun Young;Hwang, Jae Sam
    • Journal of Life Science
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    • v.26 no.6
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    • pp.737-748
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    • 2016
  • By this time, insect antimicrobial peptides (AMPs) have been characterized more than 150 peptides since purification of cecropin in the hemolymph of pupae from Hyalophora cecropia in 1980. Therefore, it is considered that insects are good sources of AMP selection. Insect AMPs are small (low molecular weight) and cationic, and amphipathic with variable length, sequence, and structure. They perform a pivotal role on humoral immunity in the insect innate immune system against invading pathogens such as bacteria, fungi, parasites, and viruses. Most of the insect AMPs are induced rapidly in the fat bodies and other specific tissues of insects after septic injury or immune challenge. Then the AMPs subsequently released into the hemolymph to act against microorganisms. These peptides have a broad antimicrobial spectrum against various microbes including anticancer activities. Insect AMPs could be divided into four families based on their structures and sequences. That is the α-helical peptides, cysteine-rich peptides, proline-rich peptides, and glycine-rich peptides/proteins. For instance, cecropins, insect defensins, proline-rich peptides, and attacins are common insect AMPs, but gloverins and moricins have been identified only in lepidopteran species. This review focuses on AMPs from insects and discusses current knowledge and recent progress with potential applications of insect AMPs.

Modulatory Effects of Herbal Medicines Extracts on Cytokine Release in Immune Response of RAW 264.7 and TK-1 (한약재 9종의 추출물이 RAW 264.7과 TK-1 세포의 cytokine 분비에 미치는 영향)

  • Bae, Su-kyoung;Cho, Se-hee;Ahn, Tae-kyu;Kim, Jee-in;Kim, Bong-hyun;Lim, Jae-hwan
    • The Journal of Internal Korean Medicine
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    • v.39 no.6
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    • pp.1244-1255
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    • 2018
  • Objectives: The purpose of this study is to determine the stimulatory effects of herbal medicines extracts on cytokines release of immune response in immune cells, RAW 264.7 and TK-1 cell. Methods: In a total of 18 extracts, 9 water extracts and 9 ethanol extracts, of herbal medicines, the quantities of polyphenolic compounds were measured and anti-oxidation activities were determined by colorimetric assay. The herbal medicine extracts were treated on RAW 264.7 and TK-1, respectively, and then the releasing changes of tumor necrosis factor-${\alpha}$ ($TNF-{\alpha}$), interleukin-6, and interleukin-10 from both immune cells were determined by the enzyme-linked immunosorbent assay. Results: The polyphenol contents were measured to be 1.56~0.64 mg/g of solids in the two types of extracts with 9 kinds of herbal medicines, while antioxidant activities were found to be 95.62~31.46% as compared with ascorbic acid control. In RAW 264.7 cells treated with herbal medicines extracts, the secretion of $TNF-{\alpha}$ increased to 1.31~1.18 fold, and the amounts of IL-6 were 68.4~97.9% compared with the control group treated with LPS alone. In particular, the secretion amount of anti-inflammatory cytokine IL-10 was suppressed by treatment using herbal medicine extracts. In the case of TK-1 cells, $TNF-{\alpha}$ secretion was suppressed according to the concentrations of herbal extract. The released amounts of IL-10 were shown at 10~40 pg/ml, and increased in a dose-dependent manner. Conclusions: Herbal medicines extracts act on macrophages inducing the secretion of inflammatory cytokine, thereby enhancing the activity of innate immunity. When acting on T cells involved in adaptive immunity, the secretion of anti-inflammatory cytokine is increased to induce the inhibition of the innate immune response.

Chicken novel leukocyte immunoglobulin-like receptor subfamilies B1 and B3 are transcriptional regulators of major histocompatibility complex class I genes and signaling pathways

  • Truong, Anh Duc;Hong, Yeojin;Lee, Janggeun;Lee, Kyungbaek;Tran, Ha Thi Thanh;Dang, Hoang Vu;Nguyen, Viet Khong;Lillehoj, Hyun S.;Hong, Yeong Ho
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.5
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    • pp.614-628
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    • 2019
  • Objective: The inhibitory leukocyte immunoglobulin-like receptors (LILRBs) play an important role in innate immunity. The present study represents the first description of the cloning and structural and functional analysis of LILRB1 and LILRB3 isolated from two genetically disparate chicken lines. Methods: Chicken LILRB1-3 genes were identified by bioinformatics approach. Expression studies were performed by transfection, quantitative polymerase chain reaction. Signal transduction was analyzed by western blots, immunoprecipitation and flow cytometric. Cytokine levels were determined by enzyme-linked immunosorbent assay. Results: Amino acid homology and phylogenetic analyses showed that the homologies of LILRB1 and LILRB3 in the chicken line 6.3 to those proteins in the chicken line 7.2 ranged between 97%-99%, while homologies between chicken and mammal proteins ranged between 13%-19%, and 13%-69%, respectively. Our findings indicate that LILRB1 and LILRB3 subdivided into two groups based on the immunoreceptor tyrosine-based inhibitory motifs (ITIM) present in the transmembrane domain. Chicken line 6.3 has two ITIM motifs of the sequence LxYxxL and SxYxxV while line 7.2 has two ITIM motifs of the sequences LxYxxL and LxYxxV. These motifs bind to SHP-2 (protein tyrosine phosphatase, non-receptor type 11) that plays a regulatory role in immune functions. Moreover, our data indicate that LILRB1 and LILRB3 associated with and activated major histocompatibility complex (MHC) class I and ${\beta}2-microglobulin$ and induced the expression of transporters associated with antigen processing, which are essential for MHC class I antigen presentation. This suggests that LILRB1 and LILRB3 are transcriptional regulators, modulating the expression of components in the MHC class I pathway and thereby regulating immune responses. Furthermore, LILRB1 and LILRB3 activated Janus kinase2/tyrosine kinase 2 (JAK2/TYK2); signal transducer and activator of transcription1/3 (STAT1/3), and suppressor of cytokine signaling 1 genes expressed in Macrophage (HD11) cells, which induced Th1, Th2, and Th17 cytokines. Conclusion: These data indicate that LILRB1 and LILRB3 are innate immune receptors associated with SHP-2, MHC class I, ${\beta}2-microglobulin$, and they activate the Janus kinase/signal transducer and activator of transcription signaling pathway. Thus, our study provides novel insights into the regulation of immunity and immunopathology.

Dietary supplementation of piperine improves innate immunity, growth performance, feed utilization and intestinal morphology of red seabream (Pagrus major)

  • Mirasha Hasanthi;G.H.T. Malintha;Kwan-Sik Yun;Kyeong-Jun Lee
    • Fisheries and Aquatic Sciences
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    • v.26 no.12
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    • pp.726-737
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    • 2023
  • Piperine, the main bioactive component of black pepper (Piper nigrum Linn.), has anti-inflammatory, antifungal, and antibacterial properties. This study evaluated the supplemental effects of piperine or black pepper on innate immunity, growth, feed utilization efficiency, and intestinal morphology in red seabream (Pagrus major). Six experimental diets were formulated, supplementing piperine at 0.0, 0.25, 0.5, 1.0, and 2.0 g/kg levels (Con, P25, P50, P100, and P200) or 1.0 g/kg black pepper (BP100). Juvenile fish (7.6 ± 0.1 g) were randomly stocked into 18 circular tanks (220 L), including 30 fish per tank. Each diet was randomly assigned to triplicate groups, and the feeding trial was conducted for 8 weeks. The results showed that final body weight, specific growth rate, weight gain, and feed utilization efficiency were significantly improved (p < 0.05) when piperine was supplemented into diets at 0.25-2.0 g/kg levels compared to the Con group. Compared to the Con diet, condition factor was significantly increased (p < 0.05) in fish fed with dietary piperine at 0.25-2.0 g/kg or BP100 diet. Serum myeloperoxidase activity was increased (p < 0.05) in P25 and P100 groups and antiprotease activity was increased (p < 0.05) in P100 group compared to the Con group. Significantly higher (p < 0.05) lysozyme activity was observed in P50, P100, P200 and BP100 groups, while total immunoglobulin level was increased in P50, P100 and BP100 groups than Con group. Superoxide dismutase activity was increased (p < 0.05) by dietary piperine at 0.25-2.0 g/kg levels and BP100 diet compared to Con diet. Plasma cholesterol was significantly lower (p < 0.05) in fish fed with piperine (0.5-2.0 g/kg) or BP100 compared to the Con diet. Compared to the Con diet significantly longer (p < 0.05) intestinal villi were observed in fish fed with piperine at 0.25-1.0 g/kg levels, and higher goblet cell count was observed in P25 and BP100 groups. Dietary inclusion of piperine would be a potent immunostimulant in fish diet and the optimum supplementation level would be 0.25-1.0 g/kg.

Anti-inflammatory Effects of Resveratrol, (-)-Epigallocatechin-3-gallate and Curcumin by the Modulation of Toll-like Receptor Signaling Pathways (Toll-like receptors 신호전달체계 조절을 통한 resveratrol, (-)-epigallocatechin-3-gallate, curcumin의 항염증 효과)

  • Youn, Hyung-Sun
    • Korean Journal of Food Science and Technology
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    • v.39 no.5
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    • pp.481-487
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    • 2007
  • Toll-like receptors (TLRs) induce innate immune responses that are essential for host defenses against invading microbial pathogens, thus leading to the activation of adaptive immune responses. In general, TLRs have two major downstream signaling pathways: the MyD88- and TRIF-dependent pathways, which lead to the activation of $NF-{\kappa}B$ and IRF3. Numerous studies have demonstrated that certain phytochemicals possessing anti-inflammatory effects inhibit $NF-{\kappa}B$ activation induced by pro-inflammatory stimuli, including lipopolysaccharides and $TNF{\alpha}$. However, the direct molecular targets for such anti-inflammatory phytochemicals have not been fully identified. Identifying the direct targets of phytochemicals within the TLR pathways is important because the activation of TLRs by pro-inflammatory stimuli can induce inflammatory responses that are the key etiological conditions in the development of many chronic inflammatory diseases. In this paper we discuss the molecular targets of resveratrol, (-)-epigallocatechin-3-gallate (EGCG), and curcumin in the TLR signaling pathways. Resveratrol specifically inhibited the TRIF pathway in TLR3 and TLR4 signaling, by targetting TBK1 and RIP1 in the TRIF complex. Furthermore, EGCG suppressed the activation of IRF3 by targetting TBK1 in the TRIF-dependent signaling pathways. In contrast, the molecular target of curcumin within the TLR signaling pathways is the receptor itself, in addition to $IKK{\beta}$. Together, certain dietary phytochemicals can modulate TLR-derived signaling and inflammatory target gene expression, and in turn, alter susceptibility to microbial infection and chronic inflammatory diseases.

Effects of Various Field Coccidiosis Control Programs on Host Innate and Adaptive Immunity in Commercial Broiler Chickens

  • Lee, Kyung-Woo;Lillehoj, Hyun S.;Jang, Seung-I.;Lee, Sung-Hyen
    • Korean Journal of Poultry Science
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    • v.39 no.1
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    • pp.17-25
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    • 2012
  • Coccidiosis control programs such as vaccines or in-feed anticoccidials are commonly practiced in the poultry industry to improve growth performance and health of commercial broiler chickens. In this study, we assessed the effects of various coccidiosis control programs (e.g., in ovo vaccination, synthetic chemicals, and antibiotic ionophores) on immune status of broiler chickens vaccinated against infectious bronchitis virus and Newcastle disease virus (ND) and raised on an Eimeria-contaminated used litter. In general, the levels of ${\alpha}$-1-acid glycoprotein, an acute phase protein, were altered by the treatments when measured at 34 days of age. Splenocyte subpopulations and serum antibody titers against ND were altered by various coccidiosis control programs. In-ovo-vaccinated chickens exhibited highest mitogenic response when their spleen cells were stimulated with concanavalin A (Con A) at 7 days of age. It is clear from this study that the type of coccidiosis control program influenced various aspects of innate and adaptive immune parameters of broiler chickens. Further studies will be necessary to delineate the underlying relationship between the type of coccidiosis control program and host immune system and to understand the role of other external environmental factors such as gut microbiota on host-pathogen interaction in various disease control programs.

Effects of Dietary Nucleotide Supplementation on the Growth Performance, Feed Utilization, Hematological Parameters and Innate Immunity in Red Seabream Pagrus major (사료 내 Nucleotides 첨가가 참돔P(agrus major)의 성장, 사료효율, 혈액성상 및 비특이적 면역반응에 미치는 영향)

  • Song, Jin-Woo;Lee, Kyeong-Jun
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.46 no.6
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    • pp.785-792
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    • 2013
  • Two studies were conducted to investigate the effects of dietary nucleotides (NT) on the growth performance, hematological parameters, and innate immune responses of red seabream Pagrus major. In Expt I, six experimental diets were formulated: a control, four that contained each NT at a level of 0.15% (inosine monophosphate, IMP; adenosine monophosphate, AMP; guanosine monophosphate, GMP; and uridine monophosphate, UMP), and one with a 1:1:1:1 mixture of NTs (IMP, AMP, GMP, and UMP). In Expt II, five experimental diets were formulated that contained 0, 0.1, 0.2, 0.4, and 1.0% IMP (commercial product). Triplicate groups of juvenile (initial body weight 33.1 g) and growing (initial body weight 120 g) red seabream were fed one of the experimental diets to apparent satiation for 8 weeks in Expt I and 12 weeks in Expt II. In Expt I, fish fed diets with NT had higher growth performance than the control group. The nitroblue tetrazolium and lysozyme activities were higher in fish fed the mixed-NT diet, and lowest in the control group. In Expt II, the final body weight and feed utilization of fish fed the 0.1% IMP diet were significantly higher than those of fish fed the control or 1.0% IMP diets. Diet palatability was improved significantly when 0.1% IMP was added. The lysozyme activity was higher in fish fed diets with 0.4-1.0% than in the control group. These results suggest that supplementation of 0.15% IMP and Mixed-NTs in diet can enhance the growth and immune responses in juvenile red seabream. The optimum IMP level appears to be 0.2% in practical feed formulation for growing red seabream.

Fcγ Receptors Modulate Pulmonary Inflammation by Activating Innate Immune Cells in Murine Hypersensitivity Pneumonitis

  • Park, Hyo Jin;Kim, Hye Sung;Chung, Doo Hyun
    • IMMUNE NETWORK
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    • v.10 no.1
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    • pp.26-34
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    • 2010
  • Background: Hypersensitivity pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled particulate antigens. The family of $Fc{\gamma}$ receptors ($Fc{\gamma}Rs$) has emerged as central regulators for modulating both pro-and anti-inflammatory responses. However, the role of $Fc{\gamma}Rs$ in the development of HP has not been investigated yet. Methods: To explore the functional roles of $Fc{\gamma}Rs$ in HP, $Fc{\gamma}R^{-/-}$ and B6 mice were challenged with Saccharopolyspora rectivirgula (SR) antigen intranasally, and compared these mice in terms of the histological change, infiltrated immune cells in BALF and in vitro immune responses. Results: $Fc{\gamma}R^{-/-}$ mice exhibited attenuation of HP in terms of histological alterations, and reduced numbers of neutrophils and macrophages in and the increased CD4 : CD8 ratio of bronchoalveolar lavage fluid. The lungs of $Fc{\gamma}R^{-/-}$ mice showed high production of Th2 cytokine such as IL-4 and slightly low production of Th1 cytokine, INF-${\gamma}$ compared to those of B6 mice. However, SR-specific adaptive immune responses of $Fc{\gamma}R^{-/-}$ mice were similar to those of B6 mice. Conclusion: These results demonstrate that activating $Fc{\gamma}$ receptors play an important role in activating neutrophils and macrophages in pulmonary inflammation and inducing Th1 differentiation by regulating cytokine expression in SR-induced HP.

Expression and regulation of avian beta-defensin 8 protein in immune tissues and cell lines of chickens

  • Rengaraj, Deivendran;Truong, Anh Duc;Lillehoj, Hyun S.;Han, Jae Yong;Hong, Yeong Ho
    • Asian-Australasian Journal of Animal Sciences
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    • v.31 no.9
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    • pp.1516-1524
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    • 2018
  • Objective: Defensins are a large family of antimicrobial peptides and components of the innate immune system that invoke an immediate immune response against harmful pathogens. Defensins are classified into alpha-, beta-, and theta-defensins. Avian species only possess beta-defensins (AvBDs), and approximately 14 AvBDs (AvBD1-AvBD14) have been identified in chickens to date. Although substantial information is available on the conservation and phylogenetics, limited information is available on the expression and regulation of AvBD8 in chicken immune tissues and cells. Methods: We examined AvBD8 protein expression in immune tissues of White Leghorn chickens (WL) by immunohistochemistry and quantitative reverse transcription-polymerase chain reaction (RT-qPCR). In addition, we examined AvBD8 expression in chicken T-, B-, macrophage-, and fibroblast-cell lines and its regulation in these cells after lipopolysaccharide (LPS) treatment by immunocytochemistry and RT-qPCR. Results: Our results showed that chicken AvBD8 protein was strongly expressed in the WL intestine and in macrophages. AvBD8 gene expression was highly upregulated in macrophages treated with different LPS concentrations compared with that in T- and B-cell lines in a time-independent manner. Moreover, chicken AvBD8 strongly interacted with other AvBDs and with other antimicrobial peptides as determined by bioinformatics. Conclusion: Our study provides the expression and regulation of chicken AvBD8 protein in immune tissues and cells, which play crucial role in the innate immunity.

Expression patterns of innate immunity-related genes in response to polyinosinic:polycytidylic acid (poly[I:C]) stimulation in DF-1 chicken fibroblast cells

  • Jang, Hyun-Jun;Song, Ki-Duk
    • Journal of Animal Science and Technology
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    • v.62 no.3
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    • pp.385-395
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    • 2020
  • Polyinosinic:polycytidylic acid (poly[I:C]) can stimulate Toll-like receptor 3 (TLR3) signaling pathways. In this study, DF-1 cells were treated with poly(I:C) at various concentrations and time points to examine the comparative expression patterns of innate immune response genes. The viability of DF-1 cells decreased from 77.41% to 38.68% when cells were treated different dose of poly(I:C) from 0.1 ㎍/mL to 100 ㎍/mL for 24 h respectively. The expressions of TLR3, TLR4, TLR7, TLR15, TLR21, IL1B, and IL10 were increased in dose- and time-dependent manners by poly(I:C) treatment. On the contrary, the expression patterns of interferon regulatory factors 7 (IRF7), Jun proto-oncogene, AP-1 transcription factor subunit (JUN), Nuclear Factor Kappa B Subunit 1 (NF-κB1), and IL8L2 were varied; IRF7 and IL8L2 were increasingly expressed whereas the expressions of JUN and NF-κB1 were decreased in a dose-dependent manner after they were early induced. In time-dependent analysis, IRF7 expression was significantly upregulated from 3 h to 24 h, whereas JUN and NF-κB1 expressions settled down from 6 h to 24 h after poly(I:C) treatment although they were induced at early time from 1 h to 3 h. Poly(I:C) treatment rapidly increased the expression of IL8L2 from 3 h to 6 h with a plateau at 6 h and then the expression of IL8L2 was dramatically decreased until 24 h after poly(I:C) treatment although the expression level was still higher than the non-treated control. These results may provide the basis for understanding host response to viral infection and its mimicry system in chickens.