Effect of Hot Water Extract from Agaricus Blazei Murill on Chemotaxis of Neutrophils

Hot water extract from the edible Brazilian mushroom, Agaricus Blazei Murill (ABM), is used for both traditional and alternative medicine. ABM is reported to stimulate anti-tumor, anti-infection, and immune activity. However, there are few reports of how ABM affects neutrophils. Therefore, in this study, we examined the effect of hot water ABM extract on neutrophil migration, phagocytosis, and reactive oxygen species production using neutrophils from guinea pig. Migratory direction and velocity as indicators of chemotactic activity of neutrophils were significantly (p 0.001) increased at concentration of 50 and 100 mg/ml in ABM extract compared with control. Phagocytic activity of neutrophil was significantly (p 0.01) increased at concentration of 5 mg/ml in ABM extract compared with control. Production of reactive oxygen species (ROS: H2O2 or ) by neutrophils was significantly (p 0.01) increased at concentration of 5 mg/ml in ABM extract compared with control. These results suggest that enhancement in neutrophil chemotactic activity, phagocytic activity and ROS production are mechanisms by which ABM extract inhibits bacterial infection in the skin and dermatitis.

Alveolar macrophage functions and DNA damage in cigarette smoke-exposed mice

Alveolar macrophages (AM) are known to play an essential role in lung defense through their ability to remove the foreign matters reaching the lung alveoli. Cigarette smoke (CS) is a critical risk factor for many lung diseases. CS is inhaled into the lung by respiretion and affects AM. It has been previously reported that CS induces inhibition of cytokine production, cell surface receptor expression and antigen presentation in AM. However, the relationship of immune suppression and DNA damage caused by CS in AM is still unclear. Therefore, in this study, we investigated AM immune function and DNA damage in CS-exposed mice. Mice were exposed to CS of 20 cigarettes/day during 10 days using a HambrugⅡsmoking machine. After exposure, AM were obtained by bronchoalveolar lavage. The number of AM was significantly increased in CS-exposed mice compared with non-CS-exposed mice. Phagocytic activity of AM was significantly inhibited by CS exposure. Percentage of CD11b-, CD14-, Toll-like receptor (TLR)2- or TLR4-positive cells was significantly decreased in CS-exposed mice compared with non-CS-exposed mice. Interleukin-1β mRNA expression in lipopolysaccharide-stimulated AM was significantly inhibited by CS exposure. Intracellular reactive oxygen species (ROS) (, H2O2) production of AM was significantly increased, and DNA damage was induced by CS exposure. These results suggest that impaired immune functions by CS exposure may be related to DNA damage via excessive ROS induced by CS. These alterations of AM caused by CS could be associated with infection and development of pulmonary diseases.

Differences in the Histopathology and Cytokine Expression Pattern between Chronological Aging and Photoaging of Hairless Mice Skin

Skin photoaging is a complex, multifactorial process resulting in functional and structural changes of the skin, and different phenotypes from chronological skin aging are well-recognized. Ultraviolet (UV)-irradiated hairless mice have been used as a skin photoaging animal model. However, differences in morphology and gene expression patterns between UV-induced and chronological skin changes in this mouse model have not been fully elucidated. Here we investigated differences in histopathology and cytokine expression between UV-irradiated and non-irradiated aged hairless mice to clarify the factor(s) that differentiate photoaging from chronological skin aging phenotypes. Eight-week-old HR-1 hairless mice were divided into UV-irradiated (UV-irradiated mice) and non-irradiated (control mice) groups. Irradiation was performed three times per week for 10 weeks. In addition, 30-week-old HR-1 hairless mice were reared until 70 weeks of age without UV irradiation (aged mice). Histopathologies revealed that the flattening of dermal-epidermal junctions and epidermal thickening were observed only in UV-irradiated mice. Decreases in fine elastic fibers just beneath the epidermis, the thickening of elastic fibers in the reticular dermis, and the accumulation of glycosaminoglycans were more prominent in UV-irradiated mice as compared to non-irradiated aged mice. Quantitative PCR analyses revealed that UV-irradiated mice showed an increase in the expression of IFN-γ. In contrast, aged mice exhibited proportional up-regulation of both pro-inflammatory and anti-inflammatory cytokines. The IFN-γ/IL-4 ratio, an indicator for the balance of pro-inflammatory and anti-inflammatory cytokines, was significantly higher in UV-irradiated mice as compared to control and non-irradiated aged mice. An elevated IFN-γ/IL-4 ratio was also observed in aged senescence-accelerated mouse-prone 1 (SAMP1) mice, a spontaneous skin photoaging model we recently reported. Thus, an imbalance between pro-inflammatory and anti-inflammatory cytokines might be a key factor to differentiate photoaged skin from chronologically-aged skin.