Purpose: Asthma is a chronic airway inflammatory disorder and is associated with macrophages. Statin, a well-known lipid-lowering agent, has recently been noted for its anti-inflammatory effect on macrophage. This study was designed to evaluate the antiasthmatic effect of atorvastatin via modulation of macrophage activation by using an animal model of allergic asthma. Methods: Atorvastatin 40 mg/kg was given by gavage once a day for 3 days before challenge of ovalbumin (OVA); airway hyperresponsiveness (AHR), airway inflammatory cells, and cytokines were evaluated in the murine asthma model. The direct effect of atorvastatin on the activation of macrophages In vitro was determined using the alveolar macrophage cell line CRL-2456. Results: Administration of atorvastatin reduced the numbers of total inflammatory cells, macrophages, and eosinophils as well as lung histology enhanced in the murine asthma model. AHR measured by enhanced pause was significantly reduced after atorvastatin administration in the murine asthma model (P< 0.05). Atorvastatin administration resulted in the reduction in serum OVA-specific IgE levels and the increase in serum OVA-specific IgG2a levels (P< 0.05). The mRNA levels of Ccr3, Il-17, and Muc5ac enhanced by OVA challenge were decreased by treatment with atorvastatin (P< 0.05). Along with these improvement in allergic inflammatory changes, the population of CD11c-CD206+ macrophages as well as the expression of Ym-1 and Relm-α in the lungs were reduced with atorvastatin (P< 0.05). In vitro test with CRL-2456 showed that atorvastatin reduced the expression of Cd206, Arg-1, and Fgf-2 induced by IL-4 stimulation (P< 0.05). Conclusion This study highlighted the antiasthmatic effect of atorvastatin on the suppression of M2 macrophage activation in allergic asthma.

OBJECTIVE: To compare the reliability and validity of the Korean range of motion standard protocol (KRSP) for measuring joint range of motion (ROM) with those of the conventional ROM measurement using a goniometer.METHODS: We conducted a randomized controlled trial involving 91 healthy elderly individuals. We compared two strategies of measuring joint ROM to evaluate the reliability and validity of each standardized protocol: first, the KRSP based on the Chungnam National University guidelines and second, handheld goniometric measurement. In the first strategy, 3 examiners (1 rehabilitation doctor, 1 physical therapist, and 1 physical therapy student) independently measured joint ROM in 46 randomly selected subjects; in the second strategy, another 3 examiners (1 rehabilitation doctor, 1 physical therapist, and 1 physical therapy student) measured joint ROM in 45 randomly selected subjects. The reliability of each protocol was calculated using intraclass correlation coefficient, ICC(2,1), and root mean square error (RMSE).RESULTS: Both protocols showed good to excellent intra-rater reliability. With goniometer use, the inter-rater reliability was low—ICC(2,1), 95% confidence interval ranged from 0.643 (0.486–0.783) to -0.078 (-0.296–0.494)— and RMSE was high. With the KRSP, the inter-rater reliability ranged from 0.846 (0.686–0.931) to 0.986 (0.972–0.994) and RMSE was low.CONCLUSION: ROM measurements using the KRSP showed excellent reliability. These results indicate that this protocol can be the reference standard for measuring ROM in clinical settings as an alternative to goniometers.
Aged ; Chungcheongnam-do ; Humans ; Joints ; Methods ; Physical Therapists ; Range of Motion, Articular ; Rehabilitation ; Reproducibility of Results

Most known osteoporosis medicines are effective for bone resorption, and so there is an increasing demand for medicines that stimulate bone formation. Watercress (N. officinale R. Br.) is widely used as a salad green and herbal remedy. This study analyzed a watercress extract using ultra-performance liquid chromatography/mass spectrometry, and identified a rutin as one of its major constituents. Osteogenic-related assays were used to compare the effects of watercress containing rutin (WCR) and rutin alone on the proliferation and differentiation of human osteoblast-like MG-63 cells. The reported data are expressed as percentages relative to the control value (medium alone; assigned as 100%). WCR increased cell proliferation to 125.0+/-4.0% (mean+/-SD), as assessed using a cell viability assay, and increased the activity of alkaline phosphatase, an early differentiation marker, to 222.3+/-33.8%. In addition, WCR increased the expression of collagen type I, another early differentiation marker, to 149.2+/-2.8%, and increased the degree of mineralization, a marker of the late process of differentiation, to 122.9+/-3.9%. Rutin alone also increased the activity of ALP (to 154.4+/-12.2%), the expression of collagen type I (to 126.6+/-6.2%), and the degree of mineralization (to 112.3+/-5.0%). Daidzein, which is reported to stimulate bone formation, was used as a positive control; the effects of WCR on proliferation and differentiation were significantly greater than those of daidzein. These results indicate that WCR and rutin can both induce bone formation via the differentiation of MG-63 cells. This is the first study demonstrating the effectiveness of either WCR or rutin as an osteoblast stimulant.
Alkaline Phosphatase ; Bone Resorption ; Cell Proliferation ; Cell Survival ; Collagen Type I ; Humans ; Osteoblasts ; Osteogenesis ; Osteoporosis ; Rutin* ; Spectrum Analysis

We recently reported a Philyra pisum lectin (PPL) that exerts mitogenic effects on human lymphocytes, and its molecular characterization. The present study provides a more detailed characterization of PPL based on the results from a monosaccharide analysis indicating that PPL is a glycoprotein, and circular dichroism spectra revealing its estimated alpha-helix, beta-sheet, beta-turn, and random coil contents to be 14.0%, 39.6%, 15.8%, and 30.6%, respectively. These contents are quite similar to those of deglycosylated PPL, indicating that glycans do not affect its intact structure. The binding properties to different pathogen-associated molecular patterns were investigated with hemagglutination inhibition assays using lipoteichoic acid from Gram-positive bacteria, lipopolysaccharide from Gram-negative bacteria, and both mannan and beta-1,3-glucan from fungi. PPL binds to lipoteichoic acids and mannan, but not to lipopolysaccharides or beta-1,3-glucan. PPL exerted no significant antiproliferative effects against human breast or bladder cancer cells. These results indicate that PPL is a glycoprotein with a lipoteichoic acid or mannan-binding specificity and which contains low and high proportions of alpha-helix and beta-structures, respectively. These properties are inherent to the innate immune system of P. pisum and indicate that PPL could be involved in signal transmission into Gram-positive bacteria or fungi.
beta-Glucans ; Breast ; Circular Dichroism ; Fungi ; Glycoproteins ; Gram-Negative Bacteria ; Gram-Positive Bacteria ; Hemagglutination ; Humans ; Immune System ; Lipopolysaccharides ; Lymphocytes ; Mannans ; Polysaccharides ; Sensitivity and Specificity* ; Teichoic Acids ; Urinary Bladder Neoplasms

Recently the transcriptional up-regulation of human beta-defensin 2 (HBD-2) by lipopolysaccharide (LPS) was found to be associated with NF-kappaB binding site. Although the general mechanisms of NF-kappaB activation by LPS stimulation are well understood, less is known about the signal transduction pathway leading to LPS-induced NF-kappaB activation in human corneal epithelial (HCE) cells. The aim of this study was to investigate the intracellular signals involved in LPS-induced HBD-2 mRNA expression in HCE cells. Pretreatments of inhibitors for NF-kappaB, protein tyrosine kinase, p38 mitogen activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) attenuated the LPS-induced NF-kappaB DNA binding activity and HBD-2 mRNA expression. Furthermore, pretreatments with inhibitors for protein kinase C (PKC), phosphatidylcholine-phospholipase C, phosphatidylinositol-phospholipase C, or phosphatidate phosphohydrolase prevented LPS-induced HBD-2 mRNA expression and HBD-2 prmoter-driven luciferase activity. However, the increased expression of HBD-2 mRNA and the increased DNA binding activity of NF-kappaB induced by LPS were not changed by the blockage of extracellular signal-regulated kinase (ERK) and of addition of antioxidants. Forskolin, a protein kinase A (PKA) agonist did not induce HBD-2 mRNA expression. These data demonstrate that LPS-induced HBD-2 mRNA expression via NF-kappaB is, at least in part, dependent on PKC, p38 MAPK, JNK, and protein tyrosine kinase status, but appears to be independent on PKA, ERK and ROS in HCE cells. Taken together, there may be more than one signaling pathways that lead to LPS-induced up-regulation of HBD-2 mRNA expression in HCE cells.
Antioxidants ; Binding Sites ; Colforsin ; Cyclic AMP-Dependent Protein Kinases ; DNA ; Epithelial Cells* ; Humans* ; JNK Mitogen-Activated Protein Kinases ; Luciferases ; NF-kappa B ; p38 Mitogen-Activated Protein Kinases ; Phosphatidate Phosphatase ; Phosphotransferases ; Protein Kinase C ; Protein Kinases ; Protein-Tyrosine Kinases ; RNA, Messenger* ; Signal Transduction ; Up-Regulation