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Acidic polysaccharides (PL) isolated from Phellinus linteus are known to stimulate the proliferation of T lymphocytes and humoral immune functions to act as a polyclonal activator of B cells, and to inhibit tumor growth and metastasis. However, little is known about their immunomodulating effects or the effects of its mechanisms on murine bone marrow (BM)-derived dendritic cells (DC). In this study, it profoundly increased CD80, CD86, MHC I, and MHC II expression in murine, GM-CSF and IL-4 stimulated, BM-derived myeloid DC. The ability of unstimulated DC to uptake dextran was higher than that of PL- or LPS-stimulated DC. We analyzed the concentration of IL-12 secreted by DC using flow cytometry and ELISA. Untreated DC secreted a low concentration of IL-12, while PL- or LPS-stimulated DC secreted higher levels of IL-12 than untreated DC. There were no remarkable differences in the concentrations of IL-12 produced by PL- or LPS-stimulated DC. However, polymyxin B (PB; an LPS inhibitor) effectively inhibited the surface molecules and IL-12 production induced by LPS, but had no effect on the PL in DC. PL-treated DC were much more potent antigen-presenting cells in allogeneic immune response than untreated DC. PL treatment not only formed morphologically mature DC but also induced predominant migration to lymphoid tissues. Moreover, the inhibitors of protein tyrosine kinase (PTK) or protein kinase C (PKC) significantly blocked the expression of surface molecules and IL-12 production in PL-stimulated DC. Treatment of DC with PL directly induced PKC activity and phosphorylated PTK. Furthermore, CD11b and/or CD18 partially mediated PL-induced DC maturation. [Copyright &y& Elsevier]

Medicinal mushrooms are increasingly used to treat a wide variety of disease processes. Aqueous extract from the fruiting body or mycelia of Phellinus linteus has been reported to produce antitumor and immunomodulatory activities in vivo and in vitro. However, the therapeutic mechanism has not been known. In the present study, we investigated whether proteoglycan (PL) isolated from P. linteus has an effect on the immunomodulatory activities of the murine splenic lymphocytes (MSLs). Treatment with PL caused a four-fold augmentation in [3H]thymidine incorporation compared to untreated control group in MSLs. Flow cytometric analysis indicated that the affected cell population was mainly CD19+ cells, but not CD3+ cells. These data suggested that the main target of PL was the B cells, but not T cells. PL also enhanced the expression of co-stimulatory molecules, CD80 and CD86, in murine B cells in a time-dependent manner. Accordingly, we investigated if intracellular [Ca2+] and reactive oxygen intermediates (ROI) were the principal downstream components that contributed to PL-induced activation, with respect to both increases of proliferation and induction of co-stimulatory molecules. However, PL has no influence on the [Ca2+] concentration and the ROI formation in murine B cells, whereas the genistein, protein tyrosine kinase (PTK) inhibitor or staurosporine, protein kinase C (PKC), blocked the proliferation and the induction of co-stimulatory molecules, CD80 and CD86, in B cells stimulated with PL. Taken together, these data suggest that PL is a biological response modifier that stimulates proliferation and expression of co-stimulatory molecules in B cells, probably by regulating PTK and PKC signaling pathways. [Copyright &y& Elsevier]

Background: Pyrazinamide (PZA) is among the first-line drugs for the treatment of tuberculosis. In vitro, it kills semidormant mycobacteria only at low pH. The purpose of this study was to compare PZA resistance with pyrazinamidase (PZase) activity and the genotype to better understand the molecular basis of PZA resistance and to expand the profile of pncA mutations worldwide. Results: Of the 28 tested strains of Mycobacterium tuberculosis, 6 were susceptible to PZA and positive for PZase activity and had no pncA mutations. Twenty-one strains were resistant to PZA and negative for PZase activity and had mutations in the pncA gene, including 15 point mutations, 5 insertions, and 2 deletions. One strain had no mutation in the pncA gene, even though it was resistant to PZA and negative for PZase activity. Three isolates had adenine to guanine point mutations in the -11 upstream region, making this the most common type of pncA mutations in this study, with at least two different RFLP patterns. Conclusion: These data help in the understanding of the molecular basis of PZA resistance. An adenine to guanine point mutation in the -11 upstream region was the most common type of pncA mutation in our isolates. The results of pncA mutation analyses should be carefully interpreted for epidemiologic purposes. [ABSTRACT FROM AUTHOR]

Background. In a previous study, we demonstrated that the human macrophage migration inhibitory factor (MIF)-like protein (As-MIF) isolated from helminths could inhibit allergic airway inflammation via the recruitment of CD4+CD25+Foxp3+ T cells. Objective. To evaluate the clinical importance of As-MIF as an antiasthma drug, we evaluated immune responses after recombinant As-MIF (rAs-MIF) treatment in peripheral blood mononuclear cell (PBMC) cultures. Methods. PBMC was isolated from 10 patients with atopic asthma, 8 patients with nonatopic asthma, and 12 nonatopic healthy subjects, and various concentrations of rAs-MIF were transferred into the PBMC culture medium. After 3 days, we measured the levels of T helper 2 and T helper 1 cytokines via ELISA. Results. In atopic asthma, IL-4 and IL-5 production was significantly reduced in the PBMC cultures after rAs-MIF treatment. These inhibitory effects were not observed in the nonatopic asthma group. By way of contrast, IL-10 production in the PMBC cultures was significantly increased after rAs-MIF treatment in all experimental groups. Conclusion. The results of this study are similar to those previously reported in a mouse study, suggesting that As-MIF might be a candidate for the specific treatment of asthma. [ABSTRACT FROM AUTHOR]

The objective of this study was to establish a drug transport study using human nasal epithelial (HNE) cell monolayers cultured by the air-liquid interface (ALI) method using serum-free medium (BEGM:DME/F12, 50:50). The cells were developed and characterized in comparison to those that have been previously cultured by the liquid-covered culture (LCC) method. The epithelial cell monolayer cultured by the ALI method resulted in a significantly higher transepithelial electrical resistance value (3,453 ± 302 ohm × cm 2 ) that was maintained ( > 1,000 ohm × cm 2 ) for up to 20 days compared with that cultured by the LCC method. Observation by scanning electron microscopy revealed mature cilia after 2 weeks in the ALI culture, while flatten unhealthy ciliated cells were observed in the LCC method. After 21 days, higher level of MUC5AC and 8 mRNA were expressed in ALI culture which confirmed the secretory differentiation of HNE monolayers in vitro . No significant difference in the permeability coefficients of a model hydrophilic marker ( 14 C-mannitol) and a lipophilic drug (budesonide) was observed between the two conditions on day 7. The passage 2–3 of the HNE monolayer using ALI condition retained the morphology and differentiated features of normal epithelium. Thus it would be a suitable model for in vitro nasal drug delivery studies. [ABSTRACT FROM AUTHOR]

An abstract of the article "Relationship Between Depression and Disease Severity in Patients With Chronic Obstructive Pulmonary Disease: A Comparison Between the GOLD Staging and the BODE Index" by Kiuk Kim and colleagues is presented.