Multiple sclerosis (MS) is a chronic immune-mediated inflammatory demyelinating disease of the central nervous system. Interferon-β (IFN-β) has been used as the first line therapy for MS treatment in Japan, but patients treated with IFN-β may develop antibodies, known as neutralizing antibodies (NAbs), which abrogate its therapeutic effects. Intramuscular IFN-β 1a and subcutaneous IFN-β 1b ar...

Lysophosphatidic acid (LPA) is an important phospholipid mediator in inflammation and immunity. However, the mechanism of LPA regulation during inflammatory response is largely unknown. Autotaxin (ATX) is the key enzyme to produce extracellular LPA from lysophosphatidylcholine (LPC). In this study, we found that ATX was induced in monocytic THP-1 cells by TLR4 ligand lipopolysaccharide (LPS), T...

Interferons (IFNs) have been tested for the therapeutic effects in various types of malignancy, but mechanisms of the anti-tumors effects and the differential biological activities among IFN members are dependent on respective cell types. In this study, we examined growth inhibitory activities of type I and III IFNs on 5 kinds of human mesothelioma cells bearing wild-type p53 gene, and showed t...

OBJECTIVE To describe detailed MRI results from 2 head-to-head phase III trials, Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis Study I (CARE-MS I; NCT00530348) and Study II (CARE-MS II; NCT00548405), of alemtuzumab vs subcutaneous interferon β-1a (SC IFN-β-1a) in patients with active relapsing-remitting multiple sclerosis (RRMS). METHODS The impact of alemtuzumab 12 mg vs...

BACKGROUND Monocytes, which are key players in innate immunity, are outnumbered by neutrophils and lymphocytes among peripheral white blood cells. The cytokine interferon-β (IFN-β) is widely used as an immunomodulatory drug for multiple sclerosis and its functional pathways in peripheral blood mononuclear cells (PBMCs) have been previously described. The aim of the present study was to identify...

Macrophages that differentiate from precursor monocytes can be polarized into a classically activated (M1) or alternatively activated (M2) status depending on different stimuli. Generally, interferon (IFN)-γ and lipopolysaccharide (LPS) are considered the classical stimuli with which to establish M1 polarization. IFN regulatory factor (IRF)1 and IFN-β are two crucial molecules involved in IFN-γ...

Although elevation of the blood glucose level is a causal adverse effect of treatment with interferon (IFN), the precise underlying molecular mechanism is largely unknown. We examined the effects of type I and type II IFN (IFN-β and IFN-γ) on insulin-induced metabolic signaling leading to glucose uptake in 3T3-L1 adipocytes. IFN-β suppressed insulin-induced tyrosine phosphorylation of IRS-1 wit...

CD4(+) Th2 development is regulated by the zinc finger transcription factor GATA3. Once induced by acute priming signals, such as IL-4, GATA3 poises the Th2 cytokine locus for rapid activation and establishes a positive-feedback loop that maintains elevated GATA3 expression. Type I IFN (IFN-α/β) inhibits Th2 cells by blocking the expression of GATA3 during Th2 development and in fully committed...

Aspergillus fumigatus is a fungal pathogen of major clinical importance. However, little is known about the role of human bronchial epithelial cells (HBECs) during A. fumigatus conidia induced inflammation. Here, we show that differentiated respiratory epithelial cells recognise inactivated resting conidia but not swollen conidia or hyphae, resulting in the induction of the interferon (IFN)-β s...

Upon treatment with vesicular stomatitis virus (VSV) particles, plasmacytoid dendritic cells (pDC) are triggered to mount substantial type I IFN responses, whereas myeloid DC (mDC) are only minor producers. Interestingly, bone marrow-derived (BM-)mDC were more vulnerable to infection with enhanced GFP (eGFP)-expressing VSV (VSVeGFP) than BM-pDC. BM-pDC stimulated with wild-type VSV mounted TLR-...