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.
Matsuo
Kaori
K
Department of Medicine and Science in Sports and Exercise, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Japan.
Zhang
Xiumin
X
Ono
Yusuke
Y
Nagatomi
Ryoichi
R