Impact of the Reticular Stress and Unfolded Protein Response on the inflammatory response in endometrial stromal cells

Grasso, Esteban; Gori, Soledad; Soczewski, Elizabeth; Fernández, Laura; Gallino, Lucila; Vota, Daiana; Martínez, Gustavo; Irigoyen, Marcela; Ruhlmann, Claudio; Lobo, Thalita Frutuoso; Salamone, Gabriela; Mattar, Rosiane; Daher, Sílvia; Leirós, Claudia Pérez

doi:10.1038/s41598-018-29779-8

Cited by 21 publications

(15 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The T-HESC cell line, derived from normal primary human ESC by telomerase immortalization, has been widely used to study several aspects of human ESC biology, including infection and cytokine production [23,24,[28][29][30][31]. T-HESC are karyotypically, morphologically, and phenotypically similar to the primary parent cells, and after treatment with estradiol and medroxyprogesterone acetate (MPA) display the morphological and biochemical pattern of decidualization [32].…”

Section: Introductionmentioning

confidence: 99%

Brucella abortus Proliferates in Decidualized and Non-Decidualized Human Endometrial Cells Inducing a Proinflammatory Response

et al. 2020

View full text Add to dashboard Cite

Brucella spp. have been associated with abortion in humans and animals. Although the mechanisms involved are not well established, it is known that placental Brucella infection is accompanied by inflammatory phenomena. The ability of Brucella abortus to infect and survive in human endometrial stromal cells (T-HESC cell line) and the cytokine response elicited were evaluated. B. abortus was able to infect and proliferate in both non-decidualized and decidualized T-HESC cells. Intracellular proliferation depended on the expression of a functional virB operon in the pathogen. B. abortus internalization was inhibited by cytochalasin D and to a lower extent by colchicine, but was not affected by monodansylcadaverine. The infection did not induce cytotoxicity and did not alter the decidualization status of cells. B. abortus infection elicited the secretion of IL-8 and MCP-1 in either decidualized or non-decidualized T-HESC, a response also induced by heat-killed B. abortus and outer membrane vesicles derived from this bacterium. The stimulation of T-HESC with conditioned media from Brucella-infected macrophages induced the production of IL-6, MCP-1 and IL-8 in a dose-dependent manner, and this effect was shown to depend on IL-1β and TNF-α. The proinflammatory responses of T-HESC to B. abortus and to factors produced by infected macrophages may contribute to the gestational complications of brucellosis.

show abstract

Section: Introductionmentioning

confidence: 99%

Brucella abortus Proliferates in Decidualized and Non-Decidualized Human Endometrial Cells Inducing a Proinflammatory Response

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Decidualized cells were stimulated with Blastocysts‐conditioned media during 48 h and Fluorochrome Inhibitor of Caspases (FAM‐FLICA ® Caspase‐1 (YVAD) Assay Kit) reagent was added for determination of caspase‐1 activation following manufacturer's instructions (Immunochemistry, Technologies, Cat. 97) as we previously described 7 . Briefly, the FLICA reagent FAM‐YVAD‐FMK enters each cell and irreversibly binds to activated caspase‐1.…”

Section: Methodsmentioning

confidence: 99%

“…This cytokine is one of the main mediators in placental viviparity and endometrium receptivity 8,9 . In fact, the pharmacological inhibition of reticulum stress‐pathway prevented not only IL‐1β production but also trophoblast invasion evaluated in an in vitro model of implantation, suggesting that IL‐1β favors a microenvironment for embryo implantation 7 . However, IL‐1β could act as a “double edge sword”: on one hand, it is a pro‐implantatory mediator; but, on the other hand, it is a powerful pro‐inflammatory factor.…”

Section: Introductionmentioning

confidence: 99%

“…Prolonged or strong reticulum stress conditions are associated with caspase‐1 inflammasome activation. This multiprotein complex is functionally active, inducing the maturation of caspase‐1 and, through this enzyme, the production of the active form of IL‐1β 7 . This cytokine is one of the main mediators in placental viviparity and endometrium receptivity 8,9 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Understanding the natural selection of human embryos: Blastocyst quality modulates the inflammatory response during the peri‐implantation period

Fernández

Grasso

Soczewski

et al. 2021

American J Rep Immunol

View full text Add to dashboard Cite

Problem Decidualized cells display an active role during embryo implantation sensing blastocyst quality, allowing the implantation of normal developed blastocysts and preventing the invasion of impaired developed ones. Here, we characterized the immune microenvironment generated by decidualized cells in response to soluble factors secreted by blastocysts that shape the receptive milieu. Method of Study We used an in vitro model of decidualization based on the Human Endometrial Stromal Cells line (HESC) differentiated with medroxiprogesterone and dibutyryl‐cAMP, then treated with human blastocysts‐conditioned media (BCM) classified according to their quality. Results Decidualized cells treated with BCM from impaired developed blastocysts increased IL‐1β production. Next, we evaluated the ability of decidualized cells to modulate other mediators associated with menstruation as chemokines. Decidualized cells responded to stimulation with BCM from impaired developed blastocysts increasing CXCL12 expression and CXCL8 secretion. The modulation of these markers was associated with the recruitment and activation of neutrophils, while regulatory T cells recruitment was restrained. These changes were not observed in the presence of BCM from normal developed blastocysts. Conclusion Soluble factors released by impaired developed blastocysts induce an exacerbated inflammatory response associated with neutrophils recruitment and activation, providing new clues to understand the molecular basis of the embryo‐endometrial dialogue.

show abstract

“…VIP triggered cAMP signaling and induced the expression of decidualization markers and chemokines whereas cells decidualized with VIP favored embryo implantation in vitro supporting its functional role. 37,38 Since decidualization depends on continuous P4 signaling and VIP induces P4 in trophoblast and stromal cells 18,39,40 it might also contribute to tissue integrity throughout this process.…”

Section: Vip As One Of the Earliest Inducers Of The Decidualization P...mentioning

confidence: 99%

From decidualization to pregnancy progression: An overview of immune and metabolic effects of VIP

Ramhorst

Grasso

Vota

et al. 2022

American J Rep Immunol

View full text Add to dashboard Cite

Background A tight immune and metabolic regulation underlies the early maternal‐placental interaction to assist the energetic dynamic demands of the fetus throughout pregnancy. The vasoactive intestinal peptide (VIP) holds biochemical, metabolic and immune properties consistent with a regulatory role during pregnancy. Aim Here we overview critical aspects of embryo implantation and placental development with special focus on the immune and metabolic effects of VIP expressed by decidual and trophoblast cells. Content During decidualization, endometrial stromal cells undergo reticular stress and trigger unfolded protein response (UPR) that enable expansion of their endoplasmic reticulum and immunomodulatory factor synthesis. These processes appear differentially affected in recurrent abortion and in vitro fertilization failure suggesting their relevance in reproductive pathologies. Similarly, defective placentation associates with altered immune, vascular and trophoblast interaction resulting in complicated pregnancies that threaten maternal and neonatal health and underlie metabolic programming of adult life. We discuss the most recent research on decidual, trophoblast and immune cell interaction on the light of VIP regulation. Its role in decidualization and UPR associated with a sterile inflammatory response and angiogenesis is discussed. Evidence on VIP modulation of cytotrophoblast cell function, metabolism and immune profile is revised as well as the shaping of decidual leukocyte phenotype and function from decidualization to term. Implications The broad spectrum of effects of VIP from implantation to term in normal and pathological conditions summarized here might contribute to the identification of novel biomarkers for diagnosis and pharmacological targeting.

show abstract

Impact of the Reticular Stress and Unfolded Protein Response on the inflammatory response in endometrial stromal cells

Cited by 21 publications

References 37 publications

Brucella abortus Proliferates in Decidualized and Non-Decidualized Human Endometrial Cells Inducing a Proinflammatory Response

Brucella abortus Proliferates in Decidualized and Non-Decidualized Human Endometrial Cells Inducing a Proinflammatory Response

Understanding the natural selection of human embryos: Blastocyst quality modulates the inflammatory response during the peri‐implantation period

From decidualization to pregnancy progression: An overview of immune and metabolic effects of VIP

Contact Info

Product

Resources

About