The aim of the present study was to examine whether amount of oral antimicrobial components, human β-defensin-2 (HBD-2), cathelicidin (LL-37), and immunoglobulin A (IgA), might be affected by prolonged strenuous exercise. Ten young male volunteers either exercised on recumbent ergometer at 75% [Formula: see text] for 60 min (exercise session) or sat quietly (resting session). Saliva samples were obtained at 60-min intervals during sessions for measurements of saliva antimicrobial components (HBD-2, LL-37, and IgA), saliva cortisol and osmolality. Saliva flow rate was decreased and saliva osmolality was increased during the 60-min exercise. Saliva HBD-2 and LL-37 concentrations and secretion rates were increased during and after the exercise, whereas saliva IgA concentration and secretion rates were decreased after the exercise. Saliva cortisol was increased during and after the exercise. The areas under the curve of the time courses of saliva levels of HBD-2 and LL-37 were negatively correlated with those of cortisol levels in saliva. The present findings suggested that a single bout of prolonged strenuous exercise caused a transient increase in the oral HBD-2 and LL-37 levels.

Adipose-derived stem cells (ADSCs) have anti-inflammatory and regenerative properties. The purpose of this study was to investigate the effect of locally administered ADSCs in a rheumatoid arthritis (RA) mouse model. In an in vivo experiment, single-cell ADScs and three dimensionally-cultured ADSc spheroids were injected intra-articularly into the knees of RA model mice and histologically assessed. Marked improvement of synovial inflammation and articular cartilage regeneration was found in ADSCtreated mice. Proliferation, migration, and apoptosis assays of synovial fibroblasts incubated with single-cell and spheroid ADSCs were performed. The expression levels of total cytokine RNA in ADSC single cells, spheroids, and ADSC-treated inflammatory synovial fibroblasts were also evaluated by quantitative reverse transcription PCR. ADSCs suppressed the proliferation and migration of activated inflammatory cells and downregulated inflammatory cytokines. TSG-6 and TGFβ1 were significantly upregulated in ADScs compared to controls and TGFβ1 was significantly upregulated in ADSC spheroids compared to single cells. The apoptosis rate of ADSC spheroids was significantly lower than that of single-cell ADSCs. These results indicated that intra-articular administration of ADSC single cells and spheroids was effective in an RA mouse model, offering a novel approach for the development of effective localized treatments for patients with RA. Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial inflammation and degeneration of articular cartilage and bone. In previous decades, systemic therapies, including methotrexate and biological disease-modifying antirheumatic drugs, significantly improved the treatment of synovial inflammation 1. Given that RA is a systemic disease, the focus has been to develop systemic treatments for it 2 ; however, swelling persists in some joints with such treatments and the application of systemic treatment is limited due to adverse, off-target effects. Therefore, localized treatment methods are important for treating RA. Corticosteroid injections are the most widely used localized treatment for RA. Although it reduces RA-associated synovitis, repeated intra-articular corticosteroid injections can lead to the degeneration of articular cartilage 3. Other adverse effects of corticosteroids include septic arthritis, local tissue atrophy, tendon rupture, and hyperglycaemia. Consequently, the development of safe, effective, and tissue-regenerating localized therapies must be explored. Recent studies in regenerative medicine have used mesenchymal stem cells (MSCs) derived from somatic tissues such as bone marrow, muscle, blood, and adipose tissue 4,5. MSCs exert anti-inflammatory effects, modulate the immune response, and modify the local microenvironment; furthermore, studies have reported their therapeutic effects for the treatment of inflammatory and autoimmune diseases 6,7. Considering the accessibility and ethical issues associated with the use of MSCs, adipose-derived stem cells (...

To elucidate the possible involvement of nitric oxide (NO) derived from inducible NO synthase (iNOS) in the pathogenesis of patients with allergic rhinitis, we used an animal model of atopic dermatitis (AD) induced by epicutaneous sensitization and analysed the differences in ear thickness, the frequency of scratching and plasma levels of ovalbumin-specific immunoglobulin E (OVA-IgE), transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, adrenocorticotropic hormone (ACTH) and α-melanocyte-stimulating hormone (α-MSH) between control and iNOS(-/-) mice. Eight-week-old control and iNOS(-/-) male C57BL/6j mice were sensitized three times with OVA antigen. Before and after the last skin sensitization, the number of scratching incidents and the thickness of the ear were examined, and the plasma levels of OVA-IgE, α-MSH, ACTH, TGF-β and TNF-α were analysed by ELISA. Sensitization of mice with OVA resulted in increased plasma levels of OVA-IgE, α-MSH, ACTH, TGF-β and TNF-α in control, but not in iNOS(-/-) mice. The administration of l-nitro-arginine-methyl ester (l-NAME) abolished all the above changes that occurred in the control mice. In addition, iNOS(-/-) mice given α-MSH exhibited a change similar to that seen in the control, whereas iNOS(-/-) mice given ACTH, TGF-β or TNF-α did not demonstrate any changes. These results indicate that symptoms of AD such as scratching can be exacerbated by α-MSH, which is induced by iNOS-derived NO.

The aim of the present study was to examine whether amount of oral cortisol, immunoglobulin A (IgA), chromogranin A (CgA) and inflammatory cytokines, might be affected by prolonged strenuous exercise. Ten young male volunteers either exercised on recumbent ergometer at 75 % V 4 O 2 max for 60 min (exercise session) or sat quietly (resting session). Saliva samples were obtained at 60 min intervals during sessions for measurements of salivary stress markers (cortisol, IgA and CgA), salivary inflammatory cytokines, such as interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and osmolality. Saliva flow rate was decreased and saliva osmolality was increased during the 60-min exercise. Saliva cortisol and CgA concentrations and secretion rates were increased during and after the exercise, whereas saliva IgA concentration and secretion rates were decreased after the exercise. Salivary inflammatory cytokines was increased during and after the exercise. The present findings suggested a single bout of prolonged strenuous exercise caused a transient increase in the salivary cortisol, CgA and inflammatory cytokines levels, whereas salivary IgA concentration and secretion rates were decreased after the exercise. Further studies, however, are needed to delineate whether or not salivary stress markers and inflammatory cytokines may be used as biological markers to determine the host responses to acute prolonged strenuous exercise.(Jpn. J. Phys. Fitness Sports Med., 60（ 3 ）: 295-304 (2011))

Atopic dermatitis is well known to exacerbate by stress. How the influence of exercise stress on the skin symptoms in patients with atopic dermatitis has not been clarified. The purpose of our research is to investigate how different strength of exercise stress acts on atopic dermatitis. Specific pathogen-free (SPF) and conventional NC/Nga male mice were used for the experiments. Conventional mice but not SPF group spontaneously develop dermal symptom similar to that of patients with atopic dermatitis at their age of 7 weeks. They were given two types of stress, mild (20 m/min for 60 min) or strong exercise (25 m/min for 90 min), using a treadmill four times per day. The dermal symptom of the conventional group was strongly exacerbated by strong exercise but ameliorated by mild exercise. Under the standard experimental conditions, plasma concentrations of α-melanocyte-stimulating hormone (α-MSH), transforming growth factor-β (TGF-β) and substance P in conventional mice increased markedly with concomitant exacerbation of the symptom. The plasma concentrations of these proteins elevated after strong exercise but decreased after mild exercise. Under the conventional conditions, plasma levels of β-endorphin increased with time by some mechanisms enhanced by the mild exercise. These observations suggested that exercise-induced stress significantly affect the symptom of atopic dermatitis in a pivotal manner depending on the plasma levels of TGF-β, α-MSH, substance P and β-endorphin.