Therapeutic Effect and Mechanism of Action of Low-molecular-weight Whey Protein Capable of Activating Macrophages in Bovine Mastitis.

BACKGROUND/AIM: Bovine mastitis is caused by the invasion and propagation of pathogenic microorganisms into the udder and mammary gland tissues of cattle. In this study, the therapeutic effect of a low-molecular-weight whey protein (LMW-WP) on bovine mastitis was evaluated. MATERIALS AND METHODS: LMW-WP was orally, intraperitoneally, and vaginally administered to bovine with mastitis. The number of somatic cells in milk was measured 24 h before the administration of LMW-WP. The effect of LMW-WP on cytokine production was measured with a microarray that evaluates the expression of cytokines. RESULTS: In the group that received 1,000 mg intraperitoneally, the somatic cell count was reduced to less than 400,000 at the shipment standard value in three of the four udders, indicating 75% efficacy. The group that received 1,000 mg by vaginal administration showed 67% efficacy. It was confirmed that LMW-WP increased the production of cytokines such as IL-5, IL-6, IL-9, IL-12, MCP-1, and VEGF in mouse macrophage cells, but it did not show any antibacterial activity. CONCLUSION: LMW-WP may be an effective therapeutic agent for bovine mastitis.

Concentration-dependent Activation of Inflammatory/Anti-inflammatory Functions of Macrophages by Hydrolyzed Whey Protein.

BACKGROUND/AIM: Whey protein is a mixture of globulins isolated from whey and mainly composed of ß-lactoglobulin, α-lactoalbumin, and lactoferrin. In this study, whey protein was hydrolyzed using various proteases, and the macrophage activation was evaluated. MATERIALS AND METHODS: Hydrolyzed whey protein was prepared using various proteases to evaluate phagocytic activity and cytokine productivity. RESULTS: The results of SDS-PAGE and gel permeation chromatography (GPC) analysis indicated that the molecular weight of whey protein was reduced using various proteases. The hydrolyzed whey protein showed a concentration-dependent induction of macrophage phagocytic activity. In addition, the hydrolyzed whey protein significantly enhanced the production of the inflammatory cytokine, TNF-α. Production of the anti-inflammatory cytokine, IL-10, was not observed at concentrations up to 1 µg, but significant production was confirmed at 100 µg. CONCLUSION: Hydrolyzed whey protein can induce the phagocytic activity of macrophages and activation of the inflammatory/anti-inflammatory functions of the macrophages depends on the concentration of the hydrolyzed whey protein.

Degalactosylated/Desialylated Bovine Colostrum Induces Macrophage Phagocytic Activity Independently of Inflammatory Cytokine Production.

BACKGROUND/AIM: Colostrum contains antibodies, such as immunoglobulin G (IgG), immunoglobulin A (IgA) and immunoglobulin M (IgM), and, therefore, has potent immunomodulating activity. In particular, IgA has an O-linked sugar chain similar to that in the group-specific component (Gc) protein, a precursor of the Gc protein-derived macrophage-activating factor (GcMAF). In the present study, we investigated the macrophage-activating effects of degalactosylated/desialylated bovine colostrum. RESULTS: We detected the positive band in degalactosylated/ desialylated bovine colostrum by western blotting using Helix pomatia agglutinin lectin. We also found that degalactosylated/ desialylated bovine colostrum could significantly enhance the phagocytic activity of mouse peritoneal macrophages in vitro and of intestinal macrophages in vivo. Besides, degalactosylated/desialylated bovine colostrum did not mediate the production of inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß). CONCLUSION: Similar to the use of GcMAF, degalactosylated/desialylated bovine colostrum can be used as a potential macrophage activator for various immunotherapies.

Morphine-Induced Constipation Develops With Increased Aquaporin-3 Expression in the Colon via Increased Serotonin Secretion.

Aquaporin-3 (AQP3) is a water channel that is predominantly expressed in the colon, where it plays a critical role in the regulation of fecal water content. This study investigated the role of AQP3 in the colon in morphine-induced constipation. AQP3 expression levels in the colon were analyzed after oral morphine administration to rats. The degree of constipation was analyzed after the combined administration of HgCl(2) (AQP3 inhibitor) or fluoxetine (5-HT reuptake transporter [SERT] inhibitor) and morphine. The mechanism by which morphine increased AQP3 expression was examined in HT-29 cells. AQP3 expression levels in rat colon were increased during morphine-induced constipation. The combination of HgCl(2) and morphine improved morphine-induced constipation. Treatment with morphine in HT-29 cells did not change AQP3 expression. However, 5-HT treatment significantly increased the AQP3 expression level and the nuclear translocation of peroxisome proliferator-activated receptor gamma (PPARγ) 1 h after treatment. Pretreatment with fluoxetine significantly suppressed these increases. Fluoxetine pretreatment suppressed the development of morphine-induced constipation and the associated increase in AQP3 expression in the colon. The results suggest that morphine increases the AQP3 expression level in the colon, which promotes water absorption from the luminal side to the vascular side and causes constipation. This study also showed that morphine-induced 5-HT secreted from the colon was taken into cells by SERT and activated PPARγ, which subsequently increased AQP3 expression levels.

Mixed-ligand complexes of paddlewheel dinuclear molybdenum as hydrodehalogenation catalysts for polyhaloalkanes.

We developed a hydrodehalogenation reaction of polyhaloalkanes catalyzed by paddlewheel dimolybdenum complexes in combination with 1-methyl-3,6-bis(trimethylsilyl)-1,4-cyclohexadiene (MBTCD) as a non-toxic H-atom source as well as a salt-free reductant. A mixed-ligated dimolybdenum complex Mo2(OAc)2[CH(NAr)2]2 (3a, Ar = 4-MeOC6H4) having two acetates and two amidinates exhibited high catalytic activity in the presence of n Bu4NCl, in which [ n Bu4N]2[Mo2{CH(NAr)2}2Cl4] (9a), derived by treating 3a with ClSiMe3 and n Bu4NCl, was generated as a catalytically-active species in the hydrodehalogenation. All reaction processes, oxidation and reduction of the dimolybdenum complex, were clarified by control experiments, and the oxidized product, [ n Bu4N][Mo2{CH(NAr)2}2Cl4] (10a), was characterized by EPR and X-ray diffraction studies. Kinetic analysis of the hydrodehalogenation reaction as well as a deuterium-labelling experiment using MBTCD-d8 suggested that the H-abstraction was the rate-determining step for the catalytic reaction.

Dinuclear molybdenum cluster-catalyzed radical addition and polymerization reactions by tuning the redox potential of a quadruple bonded Mo2 core.

We developed dinuclear molybdenum cluster-catalyzed radical addition and polymerization reactions by tuning the redox potential of the Mo(2) core. A 2,4,6-triisopropylbenzoate-supported Mo(2) complex acts as a catalyst for radical addition reactions of polyhaloalkanes to 1-alkenes and cyclopentene, while amidinate- and guanidinate-supported Mo(2) clusters are effective catalysts for the radical polymerization reaction of methyl methacrylate.