Molecular structure and immune-stimulated transcriptional modulation of the first teleostean IFP35 counterpart from rockfish (Sebastes schlegelii)

Perera, N.C.N.,Godahewa, G.I.,Nam, B.H.,Lee, J. Academic Press 2016 FISH AND SHELLFISH IMMUNOLOGY Vol.56 No.-

<P>Interferons (IFNs) and IFN-inducible proteins play numerous physiological roles, particularly in antiviral defense mechanisms of the innate immune response with the presence of pathogens. IFN-induced protein-35 kDa (IFP35) is induced by Type II IFN (IFN-gamma); it is a cytoplasmic protein that can be trans located to the nucleus via the stimulation of IFN. In this study, we report the complete molecular characterization of the IFP35 cDNA sequence from the black rockfish in an effort to understand its role in the immune response. The coding sequence of RfIFP35 encoded a putative peptide of 371 amino acids containing two characteristic Nmi/IFP 35 domains (NIDs), which are highly conserved among its counterparts. The protein showed a molecular mass of 42.2 kDa with a theoretical pI of 5.05 and was predicted to be unstable because of its high instability index (4937). Therefore, the protein-protein interaction is essential for its stability, which may be facilitated by the intrinsically disordered regions in this protein. According to cellular location prediction, the RflFP35 protein is cytosolic. Phylogenetic analysis showed that RfIFP35 was cladded within the fish counterparts. Tissue distribution profiling revealed a ubiquitous presence of the protein in all examined tissues, with highest expression in the blood followed by the spleen tissues. The expression of RfIFP35 during immune challenge with poly I:C and lipopolysaccharide treatments affirms its putative importance in the first-line host defense system. RfIFN-gamma mRNA was significantly expressed at 6 h p.i. in blood and 3 h p.i. in the spleen following treatment with different immune stimulants, and its expression was higher compared to that of RfIFP35 mRNA. Therefore, the modulation patterns of both RfIFP35 and RfIFN-gamma suggest that RfIFP35 may be induced by RfEN-gamma. (C) 2016 Elsevier Ltd. All rights reserved.</P>

Immunization of Mice with Recombinant Brucella abortus Organic Hydroperoxide Resistance (Ohr) Protein Protects Against a Virulent Brucella abortus 544 Infection

( Huynh Tan Hop ),( Alisha Wehdnesday Bernardo Reyes ),( Hannah Leah Tadeja Simborio ),( Lauren Togonon Arayan ),( Won Gi Min ),( Hu Jang Lee ),( Jin Ju Lee ),( Hong Hee Chang ),( Suk Kim ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.1

In this study, the Brucella abortus ohr gene coding for an organic hydroperoxide resistance protein (Ohr) was cloned into a maltose fusion protein expression system (pMAL), inserted into Escherichia coli, and purified, and its immunogenicity was evaluated by western blot analysis using Brucella-positive mouse sera. The purified recombinant Ohr (rOhr) was treated with adjuvant and injected intraperitoneally into BALB/c mice. A protective immune response analysis revealed that rOhr induced a significant increase in both the IgG1 and IgG2a titers, and IgG2a reached a higher level than IgG1 after the second and third immunizations. Additionally, immunization with rOhr induced high production of IFN-γ as well as proinflammatory cytokines such as TNF, MCP-1, IL-12p70, and IL-6, but a lesser amount of IL-10, suggesting that rOhr predominantly elicited a cell-mediated immune response. In addition, immunization with rOhr caused a significantly higher degree of protection against a virulent B. abortus infection compared with a positive control group consisting of mice immunized with maltose-binding protein. These findings showed that B. abortus rOhr was able to induce both humoral and cell-mediated immunity in mice, which suggested that this recombinant protein could be a potential vaccine candidate for animal brucellosis.

Immune-related Adverse Events: Overview and Management Strategies for the Use of Immune Checkpoint Inhibitors

정희철,Se Eung Oh,김지형 대한류마티스학회 2019 대한류마티스학회지 Vol.26 No.4

Recent studies on T cell immunology have been instrumental in developing therapies to overcome cancer immune escape, and immune checkpoint inhibitors have emerged as one of the most promising therapeutic tools in advanced cancer patients. Immune checkpoint inhibitors (ICPIs) are monoclonal antibodies that modulate the effects of immune checkpoints. These include cytotoxic T lymphocyte antigen 4 and programmed cell death protein 1, which are co-inhibitory signals responsible for immune suppression. Despite their clinical benefits, ICPIs behave as general immune activators, exerting to several toxic effects called immune-related adverse events attributed to organ-specific inflammation. Here, we review ICPI toxicities, highlighting the importance of their early identification and proper management.

우유 단백질과 알레르기

남명수 ( Myoung Soo Nam ) 한국유가공기술과학회 2010 Journal of Dairy Science and Biotechnology (JMSB) Vol.28 No.1

Food allergy is defined as adverse reactions toward food mediated by aberrant immune mechanisms. Therefore, an allergic response to a food antigen can be thought of as an aberrant mucosal immune response. Food allergy most often begins in the first 1~2 years of life with the process of sensitization by which the immune system responds to specific food proteins, most often with the development of allergen-specific immunoglobulin E (IgE). Over time, most food allergeies are lost, although allergy to some foods is often long lived. The most important allergen sources involved in early food allergy are milk, eggs, peanut, soybean, meat, fish and cereals. Milk allergy seem to be associated with casein and whey protein. Important features of proteins as allergenicity are size, abundance and stability. Strategies for the prevention of milk allergy is breast-feeding, partially hydrolysised infant formula, using of probiotics, immune components in milk, preparation of low allergenicity milk protein and allergy therapy (immune therapy).

Molecular Sensors for Plant Immunity; Pattern Recognition Receptors and Race-Specific Resistance Proteins

한상욱,정호원 한국식물학회 2013 Journal of Plant Biology Vol.56 No.6

Plants have to molecularly sense invasions frompathogenic microbes to activate their built-in immune responses. There are two different types of sensor proteins, calledimmune receptors. They are the indispensible molecularinstruments to perceive non-self molecules derived frommicrobes. A genetic defect of the immune receptors fails toactivate immune responses, consequently resulting in diseasesusceptibility. In general, membrane-bound immune receptors,known to be pattern recognition receptors and exposed onthe outside of the cell, recognize microbe-associated molecularpatterns from pathogens. Intracellular immune receptors,also called plant disease resistance proteins, directly perceivepathogen-derived effectors or indirectly recognize theeffector-mediated modification of host proteins inside thecells. In this review, we introduce the classes and functionsof pattern recognition receptors that were molecularly identifiedso far. Additionally, we summarize recent progresses instructural functions and molecular dynamics of the plantdisease resistance proteins.

Tunicamycin-induced endoplasmic reticulum stress suppresses plant immunity

Rupak Chakraborty,Donah Mary Macoy,이상열,김외연,김민갑 한국응용생명화학회 2017 Applied Biological Chemistry (Appl Biol Chem) Vol.60 No.6

Most secretory and membrane proteins are properly folded in the endoplasmic reticulum (ER) before being transferred to their functional destinations. Physiological and pathological stresses induce unfolded and misfolded protein accumulation in the ER, termed as ER stress. Under ER stress, cells initiate a protective response to maintain cellular homeostasis, which is referred as unfolded protein responses. Although protein processing in the ER has been known to regulate cell lifespan and disease, few evidences that prove the role of ER stress in plant immunity have been reported. We investigated the interaction between ER stress and pathogenicity in Arabidopsis by utilizing the N-glycosylation inhibitor, tunicamycin (TM) as an ER stress inducer. TM induced the accumulation of PR1 (pathogenesis-related protein 1) and callose in plant leaves, which are markers for PAMP-triggered immunity (PTI) activation. However, TM pre-treatment increased susceptibility of Arabidopsis to all bacterial pathogens tested. Moreover, TM resulted in cell death of plant leaves with an additive effect to hypersensitive response by bacterial effector proteins, suggesting TM-induced cell death is independent of the effector-triggered immunity. These results imply that TM-induced ER stress weakens overall immune system of plant not a specific immune pathway, probably via disruption of post-translational modification of immune-related proteins in the ER and subsequent cell death by apoptosis or autophagy. This study provides proves for the distinct suppressive effect of ER stress on the plant immune system.

Three novel C1q domain containing proteins from the disk abalone Haliotis discus discus: Genomic organization and analysis of the transcriptional changes in response to bacterial pathogens

Bathige, S.D.N.K.,Umasuthan, N.,Jayasinghe, J.D.H.E.,Godahewa, G.I.,Park, H.C.,Lee, J. Academic Press 2016 FISH AND SHELLFISH IMMUNOLOGY Vol.56 No.-

<P>The globular C1q (gC1q) domain containing proteins, commonly referred as C1q domain containing (C1qDC) proteins, are an essential family of proteins involved in various innate immune responses. In this study, three novel C1qDC proteins were identified from the disk abalone (Haliotis discus discus) transcriptome database and designated as AbC1qDC1, AbC1qDC2, and AbC1qDC3. The cDNA sequences of AbC1qDC1, AbC1qDC2, and AbC1qD0 consisted of 807, 1305, and 660 bp open reading frames (ORFs) encoding 269, 435, and 220 amino acids (aa), respectively. Putative signal peptides and the N-terminal gC1q domain were identified in all three AbC1qDC proteins. An additional predicted motif region, known as the coiled coil region (CCR), was identified next to the signal sequence of AbC1qDC2. The genomic organization of the AbC1qDCs was determined using a bacterial artificial chromosome (BAC) library. It was found that the CDS of AbC1qDC1 was distributed among three exons, while the CDSs of AbC1qDC2 and AbC1qDC3 were distributed between two exons. Sequence analysis indicated that the AbC1qDC proteins shared <40% identity with other counterparts from different species. According to the neighbor joining phylogenetic tree, the proteins were grouped within an invertebrate group with high evolutionary distances, which suggests that they are new members of the C1qDC family. Higher expression of AbC1qDC1 and AbC1qDC2 was detected in hepatopancreas, muscle, and mantle tissues compare to the other tissues analyzed, using reverse transcription, followed by quantitative real-time PCR (qPCR) using SYBR Green, whereas AbC1qDC3 was predominantly expressed in gill tissues, followed by muscles and the hepatopancreas. The temporal expression of AbC1qDC transcripts in gills after bacterial (Vibrio parahaemolyticus and Listeria monocytogenes) and lipopolysaccharide stimulation indicated that AbC1qDCs can be strongly induced by both Gram-negative and Gram-positive bacterial species with different response profiles. The results of this study suggest that AbC1qDCs are involved in immune responses against invading bacterial pathogens. (C) 2016 Published by Elsevier Ltd.</P>

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 Association of Animal Productio 2018 Animal Bioscience Vol.31 No.9

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.

Raw264.7 세포에서 황기와 산초 1:1 혼합물의 면역 증진 효과

조일제,유영은,이상민,김은옥,박준흠,구세광 한국응용생명화학회 2023 Journal of Applied Biological Chemistry (J. Appl. Vol.66 No.-

Present study explored immunostimulatory effects of Astragalus membranaceus and Zanthoxylum schinifolium 1:1 (w:w) mixture (AZM-1:1) in Raw264.7 cells, mouse macrophage derived cells. Treatment with 100-400 μg/mL of AZM-1:1 in Raw264.7 cells significantly increased nitric oxide production in parallel with inducible nitric oxide synthase mRNA expression without affecting cytotoxicity. In addition, AZM-1:1 dosedependently increased prostaglandin E2 production in conditioned medium along with cyclooxygenase-2 mRNA induction. Moreover, AZM-1:1 induces the transcription of tumor necrosis factor-α, interleukin-1β, interleukin-6, and monocyte chemoattractant protein-1. Immunoblot analyses revealed that AZM-1:1 significantly increased the phosphorylation of mitogen-activated protein kinases, provoked phosphorylation-mediated degradation of inhibitory-κBα, and phosphorylated p65. Furthermore, treatment with AZM-1:1 promoted phagocytosis of Escherichia coli particle labeled with green fluorescence. Taken together, AZM- 1:1 may be a promising nutraceutical for stimulation the innate immune system, including macrophages. 본 연구는 마우스 대식세포 유래 Raw264.7 세포주에서 황기와산초 1:1 혼합물(AZM-1:1)의 면역 증진 효능을 탐색하였다. Raw264.7 세포에 100-400 μg/mL의 A ZM-1:1 처치는 세포 생존율의 변화 없이 inducible nitric oxide synthase mRNA의 발현 증가와 함께 nitric oxide의 생성을 통계적으로 유의하게 증가시켰다. 더불어 A ZM-1:1은 처치 농도 의존적으로 cyclooxygenase- 2 mRNA의 유도와 함께 세포 배양액 중 prostaglandin E2의 함량을 증가시켰다. 또한, AZM-1:1은 tumor necrosis factor-α, interleukin-1β, interleukin-6 및 monocyte chemoattractant protein-1의 전사를 촉진하였다. Immunoblot 분석을 통하여AZM-1:1은 mitogen-activated protein kinase의 인산화를 증가시키고, inhibitory-κBα의 인산화를 매개한 분해를 촉진하며, p65 의 인산화를 증가시킬 수 있음을 확인하였다. AZM-1:1의 처치는 녹색 형광으로 표지된 대장균 파편의 탐식작용을 촉진하였다. 따라서, 이상의 결과는 A ZM-1:1가 대식세포를 포함한 내재면역을 증진시키는 기능성 식의약 소재가 될 수 있음을 나타낸다.

Immune-enhancing effect of Acanthopanax Koreanum and its component, Eleutheroside E on the protein-energy malnourished C57bl/6 mice

김나형,Kyu-Yeob Kim,김정아,김영호,강인철,김형민,정현자 경희대학교 융합한의과학연구소 2010 Oriental Pharmacy and Experimental Medicine Vol.10 No.3

Acanthopanax Koreanum stem (AK) has been used in Korea as a tonic and sedative as well as a drug with ginseng like activities. The purpose of our present study was to investigate the effects of AK extract (AKE) and Eleutheroside E, major component of AKE on an exacerbated immune function through utilization of protein-energy malnutrition (PEM) diet by using forced swimming test (FST). The immobility time were significantly decreased in the AKE or Eleutheroside E-administrated group compared with the control group on the FST (P < 0.05). The level of blood parameters were not changed significantly. PEM-induced weight loss of mice was reduced by oral administration of 500 mg/kg AKE. AKE oral administration improved the nutritional status such as the food efficiency ratio and the adrenal gland weight. AKE treatment significantly increased the production of interferon (IFN)-γ compared with unstimulated splenocytes but not interleukin (IL)-4. Eleutheroside E also significantly increased the IFN-γ production but not IL-2 and IL-4 in T cell line, MOLT-4 cells. These results suggest that AKE and Eleutheroside E may influence to immune-enhancing through increasing the physical endurance capacity and immune cell activation.