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Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells.

ABSTRACT: Endoplasmic reticulum (ER) stress is associated with chronic pulmonary inflammatory diseases. We hypothesized that the combined activation of both Toll-like receptor (TLR) signaling and ER stress might increase inflammatory reactions in otherwise tolerant airway epithelial cells. Indeed, ER stress resulted in an increased response of BEAS-2B and human primary bronchial epithelial cells to pathogen-associated molecular pattern stimulation with respect to IL6 and IL8 production. ER stress elevated p38 and ERK MAP kinase activation, and pharmacological inhibition of these kinases could inhibit the boosting effect. Knockdown of unfolded protein response signaling indicated that mainly PERK and ATF6 were responsible for the synergistic activity. Specifically, PERK and ATF6 mediated increased MAPK activation, which is needed for effective cytokine secretion. We conclude that within airway epithelial cells the combined activation of TLR signaling and ER stress-mediated MAPK activation results in synergistic proinflammatory activity. We speculate that ER stress, present in various chronic pulmonary diseases, boosts TLR signaling and therefore proinflammatory cytokine production, thus acting as a costimulatory danger signal.

SUBMITTER: Mijosek V

PROVIDER: S-EPMC6738801 | biostudies-other | 2016

REPOSITORIES: biostudies-other

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Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells.

Mijošek Vedrana V Lasitschka Felix F Warth Arne A Zabeck Heike H Dalpke Alexander H AH Weitnauer Michael M

Journal of innate immunity 20160716 5

Endoplasmic reticulum (ER) stress is associated with chronic pulmonary inflammatory diseases. We hypothesized that the combined activation of both Toll-like receptor (TLR) signaling and ER stress might increase inflammatory reactions in otherwise tolerant airway epithelial cells. Indeed, ER stress resulted in an increased response of BEAS-2B and human primary bronchial epithelial cells to pathogen-associated molecular pattern stimulation with respect to IL6 and IL8 production. ER stress elevated ...[more]

PMID: 27423489

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Project description:Cell-cell interactions between epithelial and stromal cells are predominant in the mammary gland, and various stromal cell-derived factors can elicit mitogenic responses in adjacent epithelial cells. Adiponectin is a hormone secreted mainly by adipocytes that mediates stromal-epithelial interactions in a number of tissues. Adiponectin receptors are expressed by bovine mammary epithelial cells, but the regulatory effects of adiponectin on the development and function of the mammary gland remain unclear. We therefore sought to investigate the effects of adiponectin on bovine mammary epithelial (MAC-T) cells and the regulatory mechanisms that underlie these adiponectin-induced actions. Our results revealed an increase in MAC-T cell proliferation and cell cycle progression in response to adiponectin. The expression of nuclear proliferating cell nuclear antigen (PCNA) and cyclin D1 was induced in MAC-T cells, and intracellular signaling molecules such as serine/threonine protein kinase (AKT), 70 kDa ribosomal S6 kinase (P70S6K), ribosomal protein S6 (S6), extracellular signal-regulated kinases 1 and 2 (ERK1/2), 90 kDa ribosomal S6 kinase (P90S6K), and cyclin D1 were activated in a dose-dependent manner. The abundance of adiponectin-induced signaling proteins was suppressed following inhibition of AKT or ERK1/2 mitogen-activated protein kinase (MAPK) signaling. In addition, inhibition of AKT or ERK1/2 signaling significantly reduced adiponectin-stimulated MAC-T cell proliferation. Furthermore, adiponectin reduced tunicamycin-induced expression and activation of endoplasmic reticulum stress-related proteins in MAC-T cells and attenuated the repressive effect of tunicamycin on proliferation of MAC-T cells. Collectively, these results suggest that adiponectin-mediated signaling may affect the development and function of the mammary gland in dairy cows by increasing mammary epithelial cell numbers. These findings may result in important implications for improving our fundamental understanding of lactation physiology in livestock species.

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Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells.

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Endoplasmic Reticulum Stress Is a Danger Signal Promoting Innate Inflammatory Responses in Bronchial Epithelial Cells.

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