-
[show abstract]
[hide abstract]
ABSTRACT: Type 1 diabetes (T1D) is caused by dysregulation of the immune system in the pancreatic islets, which eventually leads to insulin-producing pancreatic β-cell death and destabilization of glucose homeostasis. One of the major characteristics of T1D pathogenesis is the production of inflammatory mediators by macrophages that result in destruction or damage of pancreatic β-cells. In this study the inflammatory microenvironment of T1D was simulated with RAW264.7 cells and MIN6 cells, acting as macrophages and pancreatic β-cells respectably. In this setting, peroxiredoxin-1, an anti-oxidant enzyme was knocked down to observe its functions in the pathogenesis of T1D. RAW264.7 cells were primed with lipopolysaccharide and co-cultured with MIN6 cells while PRX-1 was knocked down in one or both cell types. Our results suggest that hindrance of PRX-1 activity or the deficiency of this enzyme in inflammatory conditions negatively affects pancreatic β-cell survival. The observed decrease in viability of MIN6 cells seems to be caused by nitric oxide production. Additionally, it seems that PRX-1 affects previously reported protective activity of IL-6 in pancreatic β cells as well. These results signify new, undiscovered roles for PRX-1 in inflammatory conditions and may contribute toward our understanding of autoimmunity.
Korean Journal of Physiology and Pharmacology 12/2012; 16(6):463-8. · 0.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Activated T cells express inhibitory receptors such as CTLA-4 that can downregulate immune responses. Blockade of or genetic deficiency in CTLA-4 can result in autoimmunity. Therefore, strategies to increase the inhibitory function of CTLA-4 may be attractive in settings of undesirable T cell responses such as autoimmunity or transplant rejection. We have tested the hypothesis that transgenic constitutive expression of CTLA-4 can further attenuate immune responses when compared with normal inducible expression. Our results indicate that transgenic expression of CTLA-4 in mouse T cells (CTLA-4-Tg T cells) results in reduced cell cycle progression and increased apoptosis of TCR-stimulated T cells. CTLA-4-Tg T cells display reduced T cell proliferation in an in vivo model of graft versus host disease (GVHD). These results further our understanding of how CTLA-4 can be manipulated to inhibit immune responses and may help development of new therapeutic strategies for clinical settings of autoimmunity and transplantation.
Korean Journal of Physiology and Pharmacology 10/2012; 16(5):349-53. · 0.96 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Phagocytosis and subsequent degradation of pathogens by macrophages play a pivotal role in host innate immune response to microbial infections. To find small molecule regulators for the investigation of complicated phagocytic process, we screened our in-house chemical library and found chemicals which inhibit phagocytosis of zymosan by macrophages. A representative compound 5a reduced phagocytosis of zymosan in both peritoneal macrophages and RAW264.7 cells in a dose-dependent manner. Treatment of 5a led to downregulate the key regulators of phagocytosis, Rac1, Rac2 and Cdc42, and slightly reduced phosphorylation of Akt by zymosan.
Bioorganic & medicinal chemistry 07/2012; 20(17):5262-8. · 2.82 Impact Factor
-
Tae Joon Won,
Bongjoon Kim,
Yunjung Lee,
Joon Seok Bang,
Eun Seul Oh, Jong-Sun Yoo,
Kyeong Eun Hyung,
Joowon Yoon,
Sehee Hwang,
Eon Sub Park,
So-Young Park,
Kwang Woo Hwang
[show abstract]
[hide abstract]
ABSTRACT: Lactobacillus plantarum CJLP133 was isolated from Kimchi, a Korean fermented food, and its potential to improve mouse atopic dermatitis after onset was studied. Dermatitis was developed through house dust-mite extract application onto NC/Nga mice, and then CJLP133 feeding was started. CJLP133 suppressed dermatitis-like skin lesions and decreased high serum IgE levels through balancing between IL-4 and IFN-γ in serum. CJLP133 diminished skin thickening, mast cell accumulation into inflamed site, and lymph node enlargement. In lymph node cells, CJLP133 repressed secretion of T cell cytokines such as IFN-γ, IL-4, IL-5, and IL-10. However, CJLP133 decreased ratios of IFN-γ and IL-5 to IL-10 in lymph node cells, while it did not decrease ratios of IL-4 and IL-5 to IFN-γ. Conclusively, CJLP133 exhibited therapeutic potential for atopic dermatitis in mice through orderly increment of type 1 helper T cell activation and regulatory T cell activation. These results suggest that CJLP133 could treat human atopic dermatitis.
Cellular Immunology 06/2012; 277(1-2):49-57. · 1.97 Impact Factor
-
[show abstract]
[hide abstract]
ABSTRACT: Peroxiredoxin (PRX), a scavenger of H(2) O(2) and alkyl hydroperoxides in living organisms, protects cells from oxidative stress. Contrary to its known anti-oxidant roles, the involvement of PRX-1 in the regulation of lipopolysaccharide (LPS) signaling is poorly understood, possible immunological functions of PRX-1 having been uncovered only recently. In the present study, it was discovered that the PRX-1 deficient macrophage like cell line (RAW264.7) has anti-inflammatory activity when stimulated by LPS. Treatment with LPS for 3 hrs resulted in increased gene expression of an anti-inflammatory cytokine, interleukin-10 (IL-10), in PRX-1 knock down RAW264.7 cells. Gene expression of pro-inflammatory cytokines IL-1β and tumor necrosis factor- α (TNF-α) did not show notable changes under the same conditions. However, production of these cytokines significantly decreased in PRX-1 knock down RAW264.7 cells with 12 hrs of stimulation. Production of IL-10 was also increased in PRX-1 knock down RAW264.7 cells with 12 hrs of stimulation. We predicted that higher concentrations of IL-10 would result in decreased expression of IL-1β and TNF-α in PRX-1 knock-down cells. This was confirmed by blocking IL-10, which reestablished IL-1β and TNF-α secretion. We also observed that increased concentrations of IL-10 do not affect the NF-κB pathway. Interestingly, STAT3 phosphorylation by LPS stimulation was significantly increased in PRX-1 knockdown RAW264.7 cells. Up-regulation of IL-10 in PRX-1 knockdown cells and the resulting downregulation of proinflammatory cytokine production seem to involve the STAT3 pathway in macrophages. Thus, down-regulation of PRX-1 may contribute to the suppression of adverse effects caused by excessive activation of macrophages through affecting the STAT3 signaling pathway.
Microbiology and Immunology 04/2012; 56(6):411-9. · 1.30 Impact Factor
-
Tae Joon Won,
Bongjoon Kim,
Eun Seul Oh,
Joon Seok Bang,
Yoon Jeong Lee, Jong-Sun Yoo,
Hyunmin Yu,
Joowon Yoon,
Kyeong Eun Hyung,
So-Young Park,
Kwang Woo Hwang
[show abstract]
[hide abstract]
ABSTRACT: Four Lactobacillus strains - Lactobacillus plantarum CJLP133, L. plantarum CJLP243, L. plantarum CJNR26, and Lactobacillus gasseri CJMF3 - were isolated from Korean fermented food or healthy infant feces, and their capacity to modulate cellular and humoral immune responses was studied. Feeding of the tested lactobacilli for 8 weeks did not alter the weight of and cell numbers in the spleen of mice. However, CJLP133 and CJLP243 strains increased the T lymphocyte population in the spleen of mice, while CJNR26 and CJMF3 increased the B lymphocyte population. In splenocytes treated with concanavalin A, ingestion of CJLP133 and CJLP243 promoted T lymphocyte proliferation and secretion of T cell cytokines, whereas feeding of the CJNR26 and CJMF3 strains enhanced B lymphocyte proliferation in splenocytes treated with lipopolysaccharide and plaque formation. These results suggest that CJLP133 and CJLP243 have immunostimulating activity through the enhancement of T cell activation, while CJNR26 and CJMF3 exhibit immunopotentiation through the increment of B cell activation.
Canadian Journal of Physiology and Pharmacology 06/2011; 89(6):429-34. · 1.95 Impact Factor
