Kaori Matsuo

Acute stress-induced colonic tissue HSP70 expression requires commensal bacterial components and intrinsic glucocorticoid

Induction of heat shock protein (HSPs) has a protective effect in cells under stress. Physical stressors, such as restraint, induce HSPs in colonic tissue in vivo, but the mechanism of HSP induction is not yet clear. Because commensal bacteria support basal expression of colon epithelial HSP70, we postulated that stress responses may enhance the interaction of commensal bacteria and the colonic tissue. Restraining C57BL/6 mice for 2h effectively induced HSP70 in colonic epithelia. Both blockade of stress-induced glucocorticoid by RU486 or elimination of commensal bacteria by antibiotics independently abrogated restraint-induced HSP70 augmentation. Oral administration of LPS to commensal-depleted mice restored restraint-induced HSP70 augmentation. Because TLR4 expression was absent from the epithelial surface, and was limited to lamina propria and muscularis externa, we examined how LPS reaches the lamina propria. Alexa-LPS administered in the colonic lumen was only detected in the lamina propria of the restrained mice. Expression of the tight junction component ZO-1 in the epithelia, which regulates the passage of luminal substances through the epithelia, was reduced after restraint, but reversed by RU486. In conclusion, HSP70 induction in colonic epithelial cells under restraint requires both stress-induced glucocorticoid and luminal commensal bacteria, and LPS plays a significant role. Glucocorticoid-dependent attenuation of epithelial tight junction integrity may facilitate the access of LPS into the lamina propria, where TLR4, known to be required for HSP70 induction, is abundantly expressed. Sophisticated regulation of colonic protection against stressors involving the general stress response and the luminal environment has been demonstrated.

The serine protease inhibitor camostat inhibits influenza virus replication and cytokine production in primary cultures of human tracheal epithelial cells

Abstract Background Serine proteases act through the proteolytic cleavage of the hemagglutinin (HA) of influenza viruses for the entry of influenza virus into cells, resulting in infection. However, the inhibitory effects of serine protease inhibitors on influenza virus infection of human airway epithelial cells, and on their production of inflammatory cytokines are unclear. Methods Primary cultures of human tracheal epithelial cells were treated with four types of serine protease inhibitors, including camostat, and infected with A/Sendai-H/108/2009/(H1N1) pdm09 or A/New York/55/2004(H3N2). Results Camostat reduced the amounts of influenza viruses in the supernatants and viral RNA in the cells. It reduced the cleavage of an influenza virus precursor protein, HA0, into the subunit HA1. Camostat also reduced the concentrations of the cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α in the supernatants. Gabexate and aprotinin reduced the viral titers and RNA levels in the cells, and aprotinin reduced the concentrations of TNF-α in the supernatants. The proteases transmembrane protease serine S1 member (TMPRSS) 2 and HAT (human trypsin-like protease: TMPRSS11D), which are known to cleave HA0 and to activate the virus, were detected at the cell membrane and in the cytoplasm. mRNA encoding TMPRSS2, TMPRSS4 and TMPRSS11D was detectable in the cells, and the expression levels were not affected by camostat. Conclusions These findings suggest that human airway epithelial cells express these serine proteases and that serine protease inhibitors, especially camostat, may reduce influenza viral replication and the resultant production of inflammatory cytokines possibly through inhibition of activities of these proteases.

Female scent mobilizes leukocytes to airways in BALB/c male mice.

The scent of receptive females as a signal to reproduction stimulates male mice to olfactory search of a potential breeding partner. This searching behavior is coupled with infection risk due to bacterial contamination of the fecal and urine scent marks. We hypothesized that sniffing of female soiled bedding induced the migration of immuno-competent cells into airways as a possible adaptation to breeding-related infection. Using bronchoalveolar lavage in a study on mice, we found the number of leukocytes to be significantly higher in male mice that were provided new portions of soiled bedding daily from female cages, in comparison with male mice that were kept in isolation from female scent. The number of leukocytes in blood was equal in both groups. However, monocytes were fewer in number in male mice exposed to female scent than in male mice isolated from female mice. Scent-induced migration of leukocytes was accompanied by typical behavioral (increased sniffing activity and aggressiveness) and morphological (increase preputial glands and seminal vesicles) responses to olfactory sexual stimulus.

Consideration of the prediction formula of marathon time by 20-m shuttle run test and training indexes in recreational runners

The purpose of this study is to considerate the prediction formula for marathon time based on 20-m shuttle run test and training indexes in recreational runners. 100 male and 111 female recreational runners who have experienced one or more marathon races were measured. Each participant was measured with regard to physical characteristics, 20-m shuttle run test, and answered questionnaires about his/her training (monthly running distance, frequency of training, and years of experience of running training). Moreover, participants self-reported their best marathon time. Additionally, to examine the validity of the prediction formula, 14 male and 13 female recreational runners were measured using the 20-m shuttle run test and they answered the questionnaires about his/her training. The marathon time was significantly correlated with the participant’s BMI, the times of 20-m shuttle run test, the monthly running distance, the frequency of training and the years of experience of running training for both male and female runners. Subsequently, multiple regression analysis generated the prediction model for marathon time by the measurement items. Furthermore, in the examination of the validity of the prediction formula, predicted marathon time was significantly highly correlated with measured marathon time. This study suggested that the marathon time can be predicted by the 20-m shuttle run test, the monthly running distance, and the years of experience of running training and the predicted marathon time may be useful for the marathon race and training in recreational runners. Jpn J Phys Fitness Sports Med, 67(3): 227-235 (2018)