monensin and Inflammation

Asthma is a common respiratory disease associated with airway hyperresponsiveness (AHR), airway inflammation and mast cell (MC) accumulation in the lung. Monensin, an ionophoric antibiotic, has been shown to induce apoptosis of human MCs. The aim of this study was to define the effect of monensin on MC responses, e.g., antigen induced bronchoconstriction, and on asthmatic features in models of allergic asthma. Tracheal segments from house dust mite (HDM) extract sensitized guinea pigs were isolated and exposed to monensin, followed by histological staining to quantify MCs. Both guinea pig tracheal and human bronchi were used for pharmacological studies in tissue bath systems to investigate the monensin effect on tissue viability and antigen induced bronchoconstriction. Further, an HDM-induced guinea pig asthma model was utilized to investigate the effect of monensin on AHR and airway inflammation. Monensin decreased MC number, caused MC death, and blocked the HDM or anti-IgE induced bronchoconstriction in guinea pig and human airways. In the guinea pig asthma model, HDM-induced AHR, airway inflammation and MC hyperplasia could be inhibited by repeated administration of monensin. This study indicates that monensin is an effective tool to reduce MC number and MCs are crucial for the development of asthma-like features.

Topics: Allergens; Animals; Asthma; Disease Models, Animal; Guinea Pigs; Humans; Inflammation; Mast Cells; Monensin; Pyroglyphidae

Intracellular viscosity abnormalities can lead to diabetes, neurodegenerative diseases and cancer. In this work, we developed a mitochondria-targetable fluorescent probe (EIMV) for discriminating normal and inflammatory models by viscosity changes. It was found that EIMV showed excellent properties, including high photostability, low cytotoxicity, red emission and favorable biocompatibility. In view of these unique features, this probe could successfully identify normal and cancer cells via viscosity changes. Furthermore, the EIMV probe successfully identified zebrafish with different viscosities by the same method. Moreover, EIMV exhibited different fluorescence signals in normal and inflammatory mice due to changes in viscosity. Therefore, the probe provides a new method to study the relationship between diseases and viscosity in the fields of biology and medicine.

Topics: Animals; Cell Line, Tumor; Female; Fluorescence; Fluorescent Dyes; Humans; Indoles; Inflammation; Ionophores; Mice; Mice, Inbred BALB C; Mitochondria; Monensin; Neoplasms; Nystatin; RAW 264.7 Cells; Viscosity; Zebrafish

Visfatin is a secretory protein which exerts insulin mimetic and proinflammatory effects, also functioning as an intracellular enzyme to produce NAD. Plasma visfatin levels and visfatin mRNA expression in adipose tissues are increased in obese subjects. Visfatin does not have a decent cleavable signal sequence, and the mechanism, that mediates release of visfatin from adipocytes, remains poorly understood. In this study, we demonstrate that visfatin is released abundantly into culture medium from 3T3-L1 adipocytes. Subcellular fractionation analysis showed that visfatin was localized in the cytosol, but not in nucleus, membrane, vesicles, or mitochondria fractions. Visfatin release was not reduced by Brefeldin A and Monensin, inhibitors of endoplasmic reticulum (ER)-Golgi-dependent secretion. In addition, visfatin was not released on microvesicles. These results suggest that visfatin should be released from 3T3-L1 adipocytes via an ER-Golgi or microvesicles independent pathway.

Topics: 3T3-L1 Cells; Adipocytes; Animals; Brefeldin A; Cytokines; Cytosol; Endoplasmic Reticulum; Golgi Apparatus; Inflammation; Mice; Mitochondria; Models, Biological; Monensin; Nicotinamide Phosphoribosyltransferase; RNA, Messenger