Progesterone decreases gut permeability through upregulating occludin expression in primary human gut tissues and Caco-2 cells

Abstract

Progesterone plays a protective role in preventing inflammation and preterm delivery during pregnancy. However, the mechanism involved is unknown. Microbial product translocation from a permeable mucosa is demonstrated as a driver of inflammation. To study the mechanism of the protective role of progesterone during pregnancy, we investigated the effect of physiologic concentrations of progesterone on tight junction protein occludin expression and human gut permeability in vitro and systemic microbial translocation in pregnant women in vivo . Plasma bacterial lipopolysaccharide (LPS), a representative marker of in vivo systemic microbial translocation was measured. We found that plasma LPS levels were significantly decreased during 24 to 28 weeks of gestation compared to 8 to 12 weeks of gestation. Moreover, plasma LPS levels were negatively correlated with plasma progesterone levels but positively correlated with plasma tumor necrosis factor-alpha (TNF-α) levels at 8 to 12 weeks of gestation but not at 24 to 28 weeks of gestation. Progesterone treatment increased intestinal trans-epithelial electrical resistance (TEER) in primary human colon tissues and Caco-2 cells in vitro through upregulating tight junction protein occludin expression. Furthermore, progesterone exhibited an inhibitory effect on nuclear factor kappa B (NF-κB) activation following LPS stimulation in Caco-2 cells. These results reveal a novel mechanism that progesterone may play an important role in decreasing mucosal permeability, systemic microbial translocation, and inflammation during pregnancy.

Regulation of Intestinal Barrier Function by Microbial Metabolites

“…For example, sex hormones such as estrogen and progesterone induced expression of TJ proteins and inhibited gut permeability in inflammatory organoid models from IBD patients and 2D cell line models. 200 Zhou et al 201 reported that progesterone upregulated OCLN expression in the gut and inhibited NF-κB activation to maintain gut barrier homeostasis. Irisin, a newly identified exercise hormone, was also reported to ameliorate gut barrier dysfunction via activation of the AMPK-UCP 2 pathway and binding to the integrin αVβ5 receptor.…”

The Roles of Sex Hormones in the Course of Atopic Dermatitis

“…In contrast, progesterone upregulated the expression of TJ proteins occludin and zona occludens 2 in the epidermis, and this effect was canceled by E2 in ovariectomized FvB mice [88]. Progesterone upregulated the expression of occludin in human gut tissues and Caco-2 cells [89]. It is thus hypothesized that the TJ barrier might be restored by progesterone but impaired by E2, opposite to the SC barrier, though confirmative studies are required for its verification.…”

The Combined Anti-inflammatory Strategy of Beta-2 Adrenergic Agonist and Glucocorticoid on the Laying Hen Model of Ovarian Cancer: the Immune Traits and Ovarian Inflammatory Functions

“…Progesterone, on the other hand, has been indicated to induce apoptosis and reduce cell membrane permeability that gives rise to decrease invasive potential [67]. This storied hormone has been reported to have a protective role in preventing in ammation during pregnancy by reducing of IL-6 and TNF-α, and by the recovery of antioxidant enzyme performance in some tissues [68]. Likewise, Emerging evidence has mentioned that androgen-depended pathways have also been known to plays an important role in the pathogenesis and progression of malignancies, prostate, breast, and ovarian cancers [69,70].…”