• Korean Journal of Biological Psychiatry
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• v.21 no.4
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• pp.118-127
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• 2014

Along with language, socialization is a unique feature of the human being. There is a continuous debate regarding whether the development of socialization is innate, and conducted by the environment in the growing process, or the result of the interaction of both aspects. If socialization is the result of the interaction with the environment or is an acquired developmental process, the following question rises. "Is there a 'critical period' for the development of socialization?" Although there are a huge number of studies seeking for treatment and solutions for developmental delay or deficits of socialization, it is very complicated question to answer. Historical figures such as 'Hugh Blair' of Borgue in England, and 'the wild boy of Aveyron' in France, seem to have innate socialization deficits. Nowadays patients with non-verbal learning disorder, social communication disorder, or autism spectrum disorder seem to have genetic defects. On the other hand, Harry Harlow's monkey experiments, hikikomori of Japan, Romanian orphans and patients with reactive attachment disorder seem to display social deficits due to environmental factors. However, it is not easy to clearly draw a line between innate or acquired factors. Therefore, rather than subdividing the diseases for etiological and pathophysiological approach to heterogenous groups with the common denominator of social deficit, and for the research of pathophysiology and treatment development, the authors suggest a comprehensive concept of "social dysfunction spectrum."

• Journal of Ginseng Research
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• v.41 no.3
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• pp.298-306
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• 2017

Background: Compound K (CK) is a bioactive derivative of ginsenoside Rb1 in Panax ginseng (Korean ginseng). Its biological and pharmacological activities have been studied in various disease conditions, although its immunomodulatory role in innate immunity mediated by monocytes/macrophages has been poorly understood. In this study, we aimed to elucidate the regulatory role of CK on cellular events mediated by monocytes and macrophages in innate immune responses. Methods: The immunomodulatory role of CK was explored by various immunoassays including cell-cell adhesion, fibronectin adhesion, cell migration, phagocytic uptake, costimulatory molecules, reactive oxygen species production, luciferase activity, and by the measurement of mRNA levels of proinflammatory genes. Results: Compound K induced cell cluster formation through cell-cell adhesion, cell migration, and phagocytic activity, but it suppressed cell-tissue interactions in U937 and RAW264.7 cells. Compound K also upregulated the surface expression of the cell adhesion molecule cluster of differentiation (CD) 43 (CD43) and costimulatory molecules CD69, CD80, and CD86, but it downregulated the expression of monocyte differentiation marker CD82 in RAW264.7 cells. Moreover, CK induced the release of reactive oxygen species and induced messenger RNA expression of proinflammatory genes, inducible nitric oxide synthase, and tumor necrosis factor-alpha by enhancing the nuclear translocation and transcriptional activities of nuclear factor kappa-B and activator protein-1. Conclusion: Our results suggest that CK has an immunomodulatory role in innate immune responses through regulating various cellular events mediated by monocytes and macrophages.

• Toxicological Research
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• v.33 no.4
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• pp.283-290
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• 2017

The host immune system is the first line of host defense, consisting mainly of innate and adaptive immunity. Immunity must be maintained, orchestrated, and harmonized, since overactivation of immune responses can lead to inflammation and autoimmune diseases, while immune deficiency can lead to infectious diseases. We investigated the regulation of innate and adaptive immune cell activation by Artemisia capillaris and its components (ursolic acid, hyperoside, scopoletin, and scopolin). Macrophage phagocytic activity was determined using fluorescently labeled Escherichia coli, as an indicator of innate immune activation. Concanavalin A (ConA)- and lipopolysaccharide (LPS)-induced splenocyte proliferation was analyzed as surrogate markers for cellular and humoral adaptive immunity, respectively. Neither A. capillaris water extract (WAC) nor ethanol extract (EAC) greatly inhibited macrophage phagocytic activity. In contrast, WAC suppressed ConA- and LPS-induced proliferation of primary mouse splenocytes in a dose-dependent manner. Similarly, EAC inhibited ConA- and LPS-induced splenocyte proliferation. Oral administration of WAC in mice decreased ConA- and LPS-induced splenocyte proliferation, while that of EAC suppressed LPS-induced splenocyte proliferation. Repeated administration of WAC in mice inhibited ConA- and LPS-induced splenocyte proliferation. Ursolic acid, scopoletin, and scopolin reduced ConA- and LPS-induced primary mouse splenocyte proliferation, while hyperoside did not show such activity. These results indicate that A. capillaris and its components, ursolic acid, scopoletin, and scopolin, suppress ConA- and LPS-induced adaptive immune cell activation. The results suggest that A. capillaris is useful as a regulator of adaptive immunity for diseases involving excessive immune response activation.

• Animal Bioscience
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• v.34 no.7
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• pp.1243-1252
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• 2021

Objective: An experiment was conducted to investigate the continuous and intermittent lighting program effects on terms of the productive performance, carcass traits, blood biochemical parameters, innate immune and oxidative status in broiler chicks. Methods: A total of 600 Cobb-500 one day old chicks were randomly allocated into six equal groups (100 chicks per treated group with five replicates of 20 chicks each) based on lighting program; 22 continuous lighting (22 C), 11 h lighting+1 darkness twice daily (11 L/1 D), 20 h continuous lighting (20 C), 5 h lighting+1 darkness four times daily (5 L/1 D), 18 h continuous lighting (18 C) and the final group subjected for 3 h lighting+1 h darkness six times daily (3 L/1 D). The experimental period lasted 42 days. Results: Compared with those under the intermittent light program, broiler chicks exposed to continuous lighting for 22 h had significant improvement in live body weight and carcass (dressing and breast percentage) measured traits. Though reducing lighting hours significantly reduced feed intake and feed conversion ratio values. Different lighting programs revealed no significant effect on all blood biochemical parameters. Oxidative stress and innate immunity parameters significantly enhance by reducing lighting hours (3L/1D). Conclusion: The findings suggest that reducing lighting hours up to 3L/1D would be more useful in enhancing feed efficiency, innate immunity, and oxidative status compared with continuous lighting programs on broilers.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.53 no.6
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• pp.909-917
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• 2020

This study was conducted to evaluate dietary supplementation of Sargassum horneri (SH) meal on growth performance, feed utilization, innate immunity, antioxidant capacity and disease resistance of Pacific white shrimp. The diets were added with graded levels of SH meal by 0, 0.5, 1, 2, 4 and 8% (designated as Con, SH0.5, SH1, SH2, SH4 and SH8, respectively). Quadruplicate groups of shrimp were hand-fed with one of the diets five times daily for 39 days. The innate immunity and antioxidant capacity of shrimp were significantly improved by the dietary SH supplementation. The cumulative survival of shrimp exposed to Vibrio parahaemolyticus in a challenge was higher in shrimp group fed SH diets, except for SH8, than that of shrimp fed the control diet. Growth performance and feed utilization of the shrimp were significantly decreased with the dietary SH inclusions except for 0.5%. Results indicated that dietary SH meal could be used as a functional supplement for improvements in innate immunity, antioxidant capacity and disease resistance in Pacific white shrimp. The suggested dietary inclusion level of dried SH is approximately 0.5% for the shrimp.

• Journal of Animal Science and Technology
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• v.64 no.1
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• pp.123-134
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• 2022

Toll-like receptors (TLRs), as a part of innate immunity, plays an important role in detecting pathogenic molecular patterns (PAMPs) which are structural components or product of pathogens and initiate host defense systems or innate immunity. Precise negative feedback regulations of TLR signaling are important in maintaining homeostasis to prevent tissue damage by uncontrolled inflammation during innate immune responses. In this study, we identified and characterized the function of the pancreatic progenitor cell differentiation and proliferation factor (PPDPF) as a negative regulator for TLR signal-mediated inflammation in chicken. Bioinformatics analysis showed that the structure of chicken PPDPF evolutionarily conserved amino acid sequences with domains, i.e., SH3 binding sites and CDC-like kinase 2 (CLK2) binding sites, suggesting that relevant signaling pathways might contribute to suppression of inflammation. Our results showed that stimulation with polyinosinic:polycytidylic acids (Poly [I:C]), a synthetic agonist for TLR3 signaling, increased the mRNA expression of PPDPF in chicken fibroblasts DF-1 but not in chicken macrophage-like cells HD11. In addition, the expression of pro-inflammatory genes stimulated by Poly(I:C) were reduced in DF-1 cells which overexpress PPDPF. Future studies warrant to reveal the molecular mechanisms responsible for the anti-inflammatory capacity of PPDPF in chicken as well as a potential target for controlling viral resistance.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.55 no.6
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• pp.886-893
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• 2022

This study was conducted to evaluate the effects of dietary silymarin supplementation on the growth performance, feed utilization, innate immunity and antioxidant capacity of Pacific white shrimp Litopenaeus vannamei. Four experimental diets were formulated to contain 0, 0.025, 0.05 and 0.1% silymarin (designated as Con, S0025, S005 and S01, respectively). Triplicate groups of shrimp (initial body weight: 0.70 g) were fed each of the diets for 6 weeks. After the feeding trial, weight gain and specific growth rate were significantly higher in silymarin-supplemented groups compared to Con group. Dietary silymarin significantly enhanced protein efficiency ratio of S01 group and reduced feed conversion ratio of S005 and S01 groups. Phenoloxidase and anti-protease activities were significantly higher in S01 group compared to Con group. Glutathione peroxidase and catalase activities were significantly higher in silymarin-supplemented groups compared to those of Con group. The results of this study indicate that dietary silymarin could improve the growth performance, feed utilization, innate immunity and antioxidant capacity of Pacific white shrimp. The optimum level of silymarin in diet for Pacific white shrimp is suggested to be ≥0.025%.

• Molecules and Cells
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• v.45 no.11
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• pp.833-845
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• 2022

Although asthma is a common chronic airway disease that responds well to anti-inflammatory agents, some patients with asthma are unresponsive to conventional treatment. Mesenchymal stem cells (MSCs) have therapeutic potential for the treatment of inflammatory diseases owing to their immunomodulatory properties. However, the target cells of MSCs are not yet clearly known. This study aimed to determine the effect of human umbilical cord-derived MSCs (hUC-MSCs) on asthmatic lungs by modulating innate immune cells and effector T cells using a murine asthmatic model. Intravenously administered hUC-MSCs reduced airway resistance, mucus production, and inflammation in the murine asthma model. hUC-MSCs attenuated not only T helper (Th) 2 cells and Th17 cells but also augmented regulatory T cells (Tregs). As for innate lymphoid cells (ILC), hUC-MSCs effectively suppressed ILC2s by downregulating master regulators of ILC2s, such as Gata3 and Tcf7. Finally, regarding lung macrophages, hUC-MSCs reduced the total number of macrophages, particularly the proportion of the enhanced monocyte-derived macrophage population. In a closer examination of monocyte-derived macrophages, hUC-MSCs reduced the M2a and M2c populations. In conclusion, hUC-MSCs can be considered as a potential anti-asthmatic treatment given their therapeutic effect on the asthmatic airway inflammation in a murine asthma model by modulating innate immune cells, such as ILC2s, M2a, and M2c macrophages, as well as affecting Tregs and effector T cells.

• IMMUNE NETWORK
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• v.23 no.2
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• pp.15.1-15.17
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• 2023

Innate lymphoid cells (ILCs) are critical immune-response mediators. Although they largely reside in mucosal tissues, the kidney also bears substantial numbers. Nevertheless, kidney ILC biology is poorly understood. BALB/c and C57BL/6 mice are known to display type-2 and type-1 skewed immune responses, respectively, but it is unclear whether this extends to ILCs. We show here that indeed, BALB/c mice have higher total ILCs in the kidney than C57BL/6 mice. This difference was particularly pronounced for ILC2s. We then showed that three factors contributed to the higher ILC2s in the BALB/c kidney. First, BALB/c mice demonstrated higher numbers of ILC precursors in the bone marrow. Second, transcriptome analysis showed that compared to C57BL/6 kidneys, the BALB/c kidneys associated with significantly higher IL-2 responses. Quantitative RT-PCR also showed that compared to C57BL/6 kidneys, the BALB/c kidneys expressed higher levels of IL-2 and other cytokines known to promote ILC2 proliferation and/or survival (IL-7, IL-33, and thymic stromal lymphopoietin). Third, the BALB/c kidney ILC2s may be more sensitive to the environmental signals than C57BL/6 kidney ILC2s since they expressed their transcription factor GATA3 and the IL-2, IL-7, and IL-25 receptors at higher levels. Indeed, they also demonstrated greater responsiveness to IL-2 than C57BL/6 kidney ILC2s, as shown by their greater STAT5 phosphorylation levels after culture with IL-2. Thus, this study demonstrates previously unknown properties of kidney ILC2s. It also shows the impact of mouse strain background on ILC2 behavior, which should be considered when conducting research on immune diseases with experimental mouse models.

• Journal of Ginseng Research
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• v.37 no.3
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• pp.293-299
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• 2013

20S-dihydroprotopanaxadiol (2H-PPD) is a derivative of protopanaxadiol, a glycone of ginsenosides prepared from Panax ginseng. Although ginsenosides and acidic polysaccharides are known to be major active ingredients in ginseng, the immunopharmacological activities of their metabolites and derivatives have not been fully explored. In this study, we aimed to elucidate the regulatory action of 2H-PPD on the function of monocytes and macrophages in innate immune responses. 2H-PPD was able to boost the phagocytic uptake of fluorescein isothiocyanate-dextran in macrophages and enhance the generation of radicals (reactive oxygen species) in sodium nitroprusside-treated RAW264.7 cells. The surface levels of the costimulatory molecules such as CD80 and CD86 were also increased during 2H-PPD treatment. In addition, this compound boosted U937 cell-cell aggregation induced by CD29 and CD43 antibodies, but not by cell-extracellular matrix (fibronectin) adhesion. Similarly, the surface levels of CD29 and CD43 were increased by 2H-PPD exposure. Therefore, our results strongly suggest that 2H-PPD has the pharmacological capability to upregulate the functional role of macrophages/monocytes in innate immunity.