• Parasites, Hosts and Diseases
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• v.49 no.3
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• pp.235-243
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• 2011

In order to get a better understanding of the role of protease-activated receptor 2 (PAR2) in type 2 helper T (Th2) cell responses against Trichinella spiralis infection, we analyzed Th2 responses in T. spiralis-infected PAR2 knockout (KO) mice. The levels of the Th2 cell-secreted cytokines, IL-4, IL-5, and IL-13 were markedly reduced in the PAR2 KO mice as compared to the wild type mice following infection with T. spiralis. The serum levels of parasite-specific IgE increased significantly in the wild type mice as the result of T. spiralis infection, but this level was not significantly increased in PAR2 KO mice. The expression level of thymic stromal lymphopoietin, IL-25, and eotaxin gene (the genes were recently known as Th2 response initiators) of mouse intestinal epithelial cells were increased as the result of treatment with T. spiralis excretory-secretory proteins. However, the expression of these chemokine genes was inhibited by protease inhibitor treatments. In conclusion, PAR2 might involve in Th2 responses against T. spiralis infection.

• Journal of the Korean Applied Science and Technology
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• v.37 no.4
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• pp.762-768
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• 2020

This study aimed to investigate the effect of ladder-climbing exercise training on neurobiological markers in the hippocampus of mice with type 2 diabetes (T2DM). Twenty-one C57BL/6 male mice were randomly assigned to the non-diabetic control (NDC, n = 7), diabetic control (DC, n = 7), and diabetic training (DT, n = 7) groups. The DT group performed ladder-climbing training (LCT) five times a week for eight weeks. We measured the levels of hippocampal neurobiological markers (catalase [CAT], brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], amyloid-beta [Aβ], tau, and CC motif chemokine ligand 11 [CCL11]). The BDNF levels were significantly higher in the DT group than in the DC group (p < 0.05). The Aβ and CCL11 levels were significantly higher in the DC group than in the NDC and DT groups (p < 0.05). The tau levels were significantly higher in the DC group than in the NDC group (p < 0.05). However, there was no significant difference in CAT and NGF levels among the groups (p > 0.05). These results suggest that while T2DM could induce neurodegeneration, LCT may be effective in alleviating neurodegeneration caused by T2DM.

• Journal of Microbiology and Biotechnology
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• v.23 no.1
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• pp.118-124
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• 2013

Vibrio parahaemolyticus in uncooked seafood causes acute gastroenteritis. The microorganism has two sets of type III secretion systems and two hemolysins. When it injects its effector proteins into a host cell via type III secretion system 1, one of the type III secretion systems induces secretion of interleukin (IL)-8, a proinflammatory chemokine, through the phosphorylation of ERK 1/2 and p38 MAPK. Although probiotics have beneficial effects on hosts and can help control some infectious diseases, there is little research on the efficacy of probiotics in V. parahaemolyticus infection. Here we pretreated V. parahaemolyticus-infected human intestinal epithelial cells with heat-killed Lactobacillus brevis KB290, a probiotic isolated from fermented vegetables (traditional Japanese pickles) and utilized as an ingredient of beverages and supplementary foods, and demonstrated its efficacy in enhancing IL-8 secretion from V. parahaemolyticus-infected cells. Among the three heat-killed lactic acid bacterial strains we tested, L. brevis KB290 induced the highest level of IL-8 secretions in the infected cells. Relative to control cells (Caco-2 cells pretreated with PBS), V. parahaemolyticus-infected Caco-2 cells pretreated with heat-killed L. brevis KB290 secreted IL-8 earlier, although concentrations were similar 450min after infection. Heat-killed L. brevis KB290 pretreatment also induced earlier ERK 1/2 phosphorylation, greater p38 MAPK phosphorylation, and enhanced IL-8 mRNA expression. Heat-killed L. brevis KB290 accelerated IL-8 secretion, a host cell immune response, in V. parahaemolyticus-infected cells. We consider this to be beneficial because IL-8 plays an important defensive role against infection, and would contribute to the repair of injured epithelial cells.

• Molecules and Cells
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• v.26 no.1
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• pp.67-73
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• 2008

Herpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. ExpreHerpetic stromal keratitis (HSK) is an inflammatory disorder induced by HSV-1 infection and characterized by T cell-dependent destruction of corneal tissues. It is not known what triggers $CD4^+$ T cell migration into the stroma of HSV-1-infected corneas. The keratocyte is a fibroblast-like cell that can function as an antigen-presenting cell in the mouse cornea by expressing MHC class II and costimulatory molecules after HSV-1 infection. We hypothesized that chemokines produced by stromal keratocytes are involved in $CD4^+$ T cell infiltration into the cornea. We found that keratocytes produce several cytokines and chemokines, including MCP-1, RANTES, and T cell activation (TCA)-3. HSV-1 infection increased the production of MCP-1 and RANTES by keratocytes, and these acted as chemoattractants for HSV-1-primed $CD4^+$ T cells expressing CCR2 and CCR5. Expression of MCP-1 in the corneal stroma was confirmed in vivo. Finally, when HSV-1-primed $CD4^+$ T cells were adoptively transferred into wild type and MCP-1-deficient mice that had been sublethally irradiated to minimize chemokine production from immune cells, infiltration of $CD4^+$ T cells was markedly reduced in the MCP-1-deficient mice, suggesting that it is the MCP-1 from HSV-1-infected keratocytes that attracts $CD4^+$ T cells into the cornea.

• Journal of Microbiology and Biotechnology
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• v.27 no.8
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• pp.1529-1538
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• 2017

Klebsiella pneumoniae is an opportunistic and clinically significant emerging pathogen. We investigated the relative roles of Toll-like receptor (TLR) 2 and TLR4 in initiating host defenses against K. pneumoniae. TLR2 knockout (KO), TLR4 KO, TLR2/4 double KO (DKO), and wild-type (WT) mice were inoculated with K. pneumoniae. Mice in each group were sacrificed after either 12 or 24h, and the lungs, liver, and blood were harvested to enumerate bacterial colony-forming units (CFU). Cytokine and chemokine levels were analyzed using enzyme-linked immunosorbent assay and real-time PCR, and pneumonia severity was determined by histopathological analysis. Survival was significantly shortened in TLR4 KO and TLR2/4 DKO mice compared with that of WT mice after infection with $5{\times}10^3CFU$. TLR2 KO mice were more susceptible to infection than WT mice after exposure to a higher infectious dose. Bacterial burdens in the lungs and liver were significantly higher in TLR2/4 DKO mice than in WT mice. Serum $TNF-{\alpha}$, MCP-1, MIP-2, and nitric oxide levels were significantly decreased in TLR2/4 DKO mice relative to those in WT mice, and TLR2/4 DKO mice showed significantly decreased levels of $TNF-{\alpha}$, IL-6, MCP-1, and inducible nitric oxide synthase mRNA in the lung compared with those in WT mice. Collectively, these data indicate that TLR2/4 DKO mice were more susceptible to K. pneumoniae infection than single TLR2 KO and TLR4 KO mice. These results suggest that TLR2 and TLR4 play cooperative roles in lung innate immune responses and bacterial dissemination, resulting in systemic inflammation during K. pneumoniae infection.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.12
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• pp.4893-4896
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• 2014

Background: Recent reports have shown that C-X-C chemokine receptor 4 (CXCR4) plays an important role in metastasis. Despite a clear understanding of the protein's structure and properties, its functional role remains elusive. We conducted the present study to evaluate the expressions of CXCR4 in pancreatic cancer, and to investigate its relationship with clinicopathological parameters, especially perineural invasion(PNI). Materials and Methods: The association between CXCR4 expression and perineural invasion was determined by immunohistochemistry in pancreatic cancer patients (n=51). Results: CXCR4 expression was correlated with the existence of PNI and the type of PNI (p=0.042, p=0.040). TIMP-2 expression was also correlated with the existence, the pathway and degree of PNI (p=0.000, p=0.006, p=0.000). Conclusions: Our results suggest an association between PNI and expression of CXCR4 and TIMP-2 in pancreatic cancer. CXCR4 may promote the occurrence of PNI in pancreatic cancer cells by decreasing the inhibition of TIMPs on MMP.

• International Journal of Oral Biology
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• v.47 no.4
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• pp.55-62
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• 2022

Bioactive flavonoids have been shown to improve the biological activity of stem cells derived from different sources in tissue regeneration. The goal of this study was to see how naringin, a natural flavonoid discovered in citrus fruits, affected the biological properties of human dental pulp stem cells (HDPSCs). In this study, we found that naringin increases the migratory ability of HDPSCs. Naringin increased matrix metalloproteinase-2 (MMP-2) and C-X-C chemokine receptor type 4 (CXCR4) mRNA and protein expression in HDPSCs. ARP100, a selective MMP-2 inhibitor, and AMD3100, a CXCR4 antagonist, both inhibited the naringin-induced migration of HDPSCs. Furthermore, naringin increased osteogenic differentiation of HDPSCs and the expression of the osteogenic-related marker, alkaline phosphatase in HDPSCs. Taken together, our findings suggest that naringin may be beneficial on dental tissue or bone regeneration by increasing the biological activities of HDPSCs.

• Journal of Microbiology and Biotechnology
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• v.33 no.6
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• pp.823-830
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• 2023

Lactococcus lactis is a lactic acid bacterium and used in the dairy food industry. The ameliorating effects of Lactobacillus species on atopic dermatitis (AD) have been extensively studied, but the specific effect of L. lactis strains has not yet been investigated. In this study, the efficacy of L. lactis LB 1022, isolated from natural cheese, was evaluated using RAW 264.7, HMC-1 and HaCaT cell lines and an ovalbumin-sensitized AD mouse model. L. lactis LB 1022 exhibited nitric oxide suppression and anti-allergy and anti-inflammatory activity in vitro. Oral administration of L. lactis LB 1022 to AD mice significantly reduced the levels of IgE, mast cells, and eosinophils, and a range of T cell-mediated T helper Th1, Th2, and Th17-type cytokines under interleukin (IL)-10, transforming growth factor-β (TGF-β), thymus and activation-regulated chemokine (TARC), and thymic stromal lymphopoietin (TSLP). In addition, L. lactis LB 1022 treatment increased the concentration of short-chain fatty acids. Overall, L. lactis LB 1022 significantly modulated AD-like symptoms by altering metabolites and the immune response, illustrating its potential as candidate for use in functional food supplements to alleviate AD.

• Biomedical Science Letters
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• v.20 no.3
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• pp.162-167
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• 2014

Tuberculosis (TB) is one of the major global health problems and it has been estimated that in 5~10% of Mycobacterium tuberculosis (MTB)-infected individuals, the infection progresses to an active disease. Numerous cytokines and chemokines regulate immunological responses at cellular level including stimulation and recruitment of wide range of cells in immunity and inflammation. In the present study, the mRNA expression levels of eight host immune markers containing of IFN-${\gamma}$, TNF-${\alpha}$, IL-2R, IL-4, IL-10, CXCL9, CXCL10, and CXCL11 in whole blood cells from active pulmonary TB patients were measured after T-cell mitogen (PHA) and MTB specific antigens (ESAT-6, CFP-10, and TB7.7). Among the TH1-type factors, IFN-${\gamma}$ mRNA expression was peaked at 4 h, TNF-${\alpha}$ and IL-2R mRNA expression was significantly high at the late time points (24 h) in active TB patients, TH2-type cytokine (IL4 and IL10) mRNA expression levels in both active TB and healthy controls samples did not changed significantly, and the mRNA expression of the three IFN-${\gamma}$-induced chemokines (CXCL9, CXCL10, and CXCL11) were peaked at the late time points (24 h) in active TB patients after MTB specific antigen stimulation. In conclusion, the mRNA expression patterns of the TB-related immune markers in response to the T-cell mitogen (PHA) differed from those in response to MTB specific antigens and these findings may helpful for understanding the relationship between MTB infection and host immune markers in a transcripts level.

• The Journal of the Korean Society for Microbiology
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• v.35 no.2
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• pp.117-127
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• 2000

The non-ELR-containing CXC chemokines Mig and IP-10 have been shown to function as chemotactic cytokines for activated T lymphocytes. In this study, we examined the potential involvement of Mig and IP-10 in antimycobacterial response of mice immunized or infected with M. bovis BCG. The accumulation of Mig and IP-10 mRNA in resident peritoneal monocytes ($RPM{\Phi}$) was slightly reduced by stimulation with vBCG, and the degree was greater for 24 hr culture even though IFN-${\gamma}$ was added. Expression of Mig, IP-10, and IFN-${\gamma}$ in 24 hr delayed-type hypersensitivity (DTH) response was stronger in vBCG-immune mice than in the non-immune. The increase of DTH measured by foot-pad thickness appears to be clearly related to the levels of chemokines Mig and IP10 messages and those of IFN-${\gamma}$ and IL-12. Stimulation with vBCG for 2 days decreased or completely dropped the levels of Mig message in non-immune or immune splenocytes, respectively, whereas IP-10 message was slightly decreased in 2 days culture. Moreover, messages for IL-12 (p40) showed similar kinetics for Mig. The levels of Mig and IP-10 mRNA during the course of infection with BCG were not readily changed in lungs, livers, and spleens from BCG-infected mice. Although there was no obvious changes of Mig and IP-10 messages in the target organs during infection process, we found that the infection progressed over the first 3 wk before being contained by the emerging immune response suggested from detectable amount of IFN-${\gamma}$ mRNA around this time. In view of selectivity of chemokines Mig and IP-10 for activated T cells, these data suggest that chemokine Mig and IP-10, especially in collaboration with IL-12 and IFN-${\gamma}$, may playa role as T cell recruiters in immune response against mycobacterial infection.