IK acts as an immunoregulator of inflammatory arthritis by suppressing TH17 cell differentiation and macrophage activation.

Pathogenic T helper cells (TH) and macrophages have been implicated in the development of rheumatoid arthritis (RA), which can lead to severe synovial inflammation and bone destruction. A range of therapies have been widely used for RA, including specific monoclonal antibodies and chemical inhibitors against inflammatory cytokines produced by these cells. However, these have not been sufficient to meet the medical need. Here, we show that in transgenic mice expressing truncated IK (tIK) cytokine, inflammatory arthritis symptoms were ameliorated as the result of suppression of the differentiation of TH1 and TH17 cells and of macrophage activation. During inflammatory responses, tIK cytokine systemically regulated macrophage functions and TH17 cell differentiation through inactivation of the MAPK and NF-κB pathways. Interestingly, the level of tIK cytokine was higher in synovial fluid of RA patients compared with that in osteoarthritis (OA) patients. Our observations suggest that tIK cytokine can counterbalance the induction of inflammatory cells related to RA and thus could be a new therapeutic agent for the treatment of RA.

Tracking Study About Adenovirus 36 Infection: Increase of Adiposity.

This study investigated the cross-sectional and longitudinal association between adenovirus 36 (Ad36) and obesity in 79 Korean adolescent boys over 1 year. We analyzed the changes in body composition and metabolic risk factors according to the presence of Ad36 antibodies. Ad36 antibodies in serum were detected using the constant virus-decreasing serum method. We found that the fat percentage and fasting insulin in the Ad36-seropositive group were greater than the Ad36-seronegative group. These results suggest that Ad36 infection is associated with an increase of adiposity, and the experience of Ad36 infection may affect the future fat gain of adolescents.

Adenovirus 36 attenuates weight loss from exercise but improves glycemic control by increasing mitochondrial activity in the liver.

Human adenovirus type 36 (Ad36) as an obesity agent induces adiposity by increasing glucose uptake and promoting chronic inflammation in fat tissues; in contrast, exercise reduces total body fat and inflammation. Our objective was to determine the association between Ad36 and the effects of exercise on inflammation and glycemic control. In the human trials (n = 54), Korean children (aged 12-14 years) exercised for 60 min on three occasions each week for 2 months. We compared the body mass index (BMI) Z-scores before and after exercise. C57BL/6 mice were infected with Ad36 and Ad2 as a control, and these mice exercised for 12 weeks postinfection. After the exercise period, we determined the serum parameters and assessed the presence of inflammation and the mitochondrial function in the organs. Ad36-seropositive children who were subjected to a supervised exercise regimen had high BMI Z-scores whereas Ad36-seronegative children had lower scores. Similarly, Ad36-infected mice were resistant to weight loss and exhibited chronic inflammation of their adipose tissues despite frequent exercise. However, Ad36 combined with exercise reduced the levels of serum glucose, nonesterified fatty acids, total cholesterol, and insulin in virus-infected mice. Interestingly, virus infection increased the mitochondrial function in the liver, as demonstrated by the numbers of mitochondria, cytochrome c oxidase activity, and transcription of key mitochondrial genes. Therefore Ad36 counteracts the weight-loss effect of exercise and maintains the chronic inflammatory state, but glycemic control is improved by exercise synergistically because of increased mitochondrial activity in the liver.

Reduction of adenovirus 36-induced obesity and inflammation by mulberry extract.

Adenovirus 36 (Ad36) is known to be associated with human obesity and to trigger inflammation in murine models. However, to date no clinical drugs for treating virus-induced obesity have been developed. Therefore, in this study, the anti-obesity and anti-inflammation effects of mulberry extract on Ad36 were evaluated in mice. The mulberry extract-fed group showed a reduction in total body weight and in epidermal fat pads. A combination of various mulberry components (1-deoxynojirimycin, kuromanin chloride and resveratrol) and a mulberry extract prevented viral replication by 50% and 70%, respectively, compared with an untreated Ad36-infected group. Moreover, the extract decreased both concentrations of proinflammatory cytokines, such as MCP-1 and TNF-α, and the numbers of infiltrating immune cells and macrophages in epidermal fat pads. In conclusion, dietary mulberry extract might offer an avenue for the development of therapeutic approaches for treating or preventing virus-induced obesity and inflammation-related metabolic diseases.

Obesity-induced chronic inflammation is associated with the reduced efficacy of influenza vaccine.

The relationship between obesity and vaccine efficacy is a serious issue. Previous studies have shown that vaccine efficacy is lower in the obese than in the non-obese. Here, we examined the influence of obesity on the efficacy of influenza vaccination using high fat diet (HFD) and regular fat diet (RFD) mice that were immunized with 2 types of influenza virus vaccines-cell culture-based vaccines and egg-based vaccines. HFD mice showed lower levels of neutralizing antibody titers as compared with RFD mice. Moreover, HFD mice showed high levels of MCP-1 in serum and adipocytes, and low level of influenza virus-specific effector memory CD8(+) T cells. After challenge with influenza virus, the lungs of HFD mice showed more severe inflammatory responses as compared with the lungs of RFD mice, even after vaccination. Taken together, our data suggested that the inflammatory condition in obesity may contribute to the suppressed efficacy of influenza vaccination.

Quantification of ridging in ferritic stainless steel sheets by electron backscattered diffraction R-value maps.

In ferritic stainless steel (FSS), undesirable surface defects of ridging appear during deep drawing. The formation of these defects is attributed to the inhomogeneous distribution of orientations of individual grains. In the present work, a new electron backscattered diffraction R(α)-value map was introduced, and the dependence of the tensile directions on the formation of ridging in an FSS sheet was discussed using this map. The results showed that large grain colonies in the R(α)-value maps lead to the formation of severe ridging in an FSS sheet.

Immunogenicity and safety of H1N1 influenza hemagglutinin protein expressed in a baculovirus system.

Although most influenza vaccines are produced in eggs, new types of vaccines must be developed. In this study, the immunogenicity and safety of a baculovirus-expressed hemagglutinin (HA) of H1N1 influenza virus (Korea/01/2009; designated "HA-Bac-K") was compared with those of a commercially available baculovirus-expressed HA (designated "HA-Bac-C") and an Escherichia coli-expressed HA (designated "HA-E. Coli-K"). HA-Bac-K succeeded in inducing hemagglutination inhibition and neutralization antibodies in mouse and ferret models. The different immunogenicities observed may be attributable to the different expression systems and purification protocols used. Our work suggests that HA expressed in a baculovirus system is an effective and safe candidate influenza vaccine.