Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes

Lü, Lei; Li, Tiantian; Williams, Graham D.; Petit, Elizabeth; Borowsky, Mark; Walker, W. Allan

doi:10.1152/ajpgi.00011.2010

Cited by 22 publications

(23 citation statements)

References 35 publications

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“…However, studies in various endothelial and nonintestinal epithelial cell lines provided evidence for the ability of glucocorticoids to stimulate tight junction sealing in the absence of inflammatory stimuli (14,16,36,60). A recent report furthermore described upregulation of multiple tight junction proteins by corticosteroids in immature enterocytes as part of their well-known ability to promote intestinal maturation (23). The aim of our study, therefore, was to investigate whether glucocorticoids regulate barrier characteristics of the intestinal epithelium in the absence of immunological factors using an in vitro model.…”

mentioning

confidence: 99%

Glucocorticoids regulate barrier function and claudin expression in intestinal epithelial cells via MKP-1

Fischer

Gluth

Weege

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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Barrier dysfunction is pivotal to the pathogenesis of inflammatory bowel diseases (IBD) and collagenous colitis. Glucocorticoids restore barrier function in Crohn's disease, but whether this reflects attenuated inflammation or an epithelial-specific action has not yet been addressed. Using filter-grown Caco-2 monolayers as an in vitro model of the intestinal epithelial barrier, we observed that glucocorticoids induced a time- and dose-dependent increase in transepithelial electrical resistance (TEER) in a glucocorticoid receptor-dependent manner without altering flux of larger solutes or changing principal tight junction architecture. This was accompanied by reduced paracellular cation flux, reduced expression of the pore-forming tight junction component claudin-2, and upregulation of the sealing tight junction protein claudin-4. In contrast, expression of occludin, claudin-1, -7, or -8 was not altered. Dexamethasone increased expression and activity of MAPK phosphatase-1 and inhibition of this phosphatase prevented the glucocorticoid-induced changes in TEER and claudin expression, whereas inhibiting p38 or MEK1/2 was not sufficient to replicate the glucocorticoid effects. Upon exposure to IFN-γ, TNF-α, or IL-1β, TEERs declined in dexamethasone-treated cells but remained consistently higher than in cells not receiving glucocorticoids. Treatment with IFN/TNF resulted in an upregulation of claudin-2 that was significantly attenuated by dexamethasone, whereas increased claudin-2 expression upon IL-1β stimulation was not affected by glucocorticoids. Taken together, barrier augmentation might represent a previously unrecognized mechanism of action, potentially contributing to the therapeutic efficacy of glucocorticoids in IBD and collagenous colitis.

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mentioning

confidence: 99%

Glucocorticoids regulate barrier function and claudin expression in intestinal epithelial cells via MKP-1

Fischer

Gluth

Weege

et al. 2014

American Journal of Physiology-Gastrointestinal and Liver Physi

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“…The overall in vitro response of human intestinal epithelial cells to GCs was also studied using microarray analysis. This work showed that hydrocortisone differ entially regulates the expression levels of protein encoding genes and enterocyte markers involved in polarization and tight junction formation [56]. Altogether, these studies underlined that both endogenous (adrenal derived) and exogenous GCs play a role dur ing the functional maturation of the gut and the maintenance of intestinal epithelial barrier function.…”

Section: Function and Roles Of Intestinal Gcsmentioning

confidence: 67%

Intestinal steroidogenesis

et al. 2015

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a b s t r a c tSteroids are fundamental hormones that control a wide variety of physiological processes such as metabolism, immune functions, and sexual characteristics. Historically, steroid synthesis was considered a function restricted to the adrenals and the gonads. In the past 20 years, a significant number of studies have demonstrated that steroids could also be synthesized or metabolized by other organs. According to these studies, the intestine appears to be a major source of de novo produced glucocorticoids as well as a tissue capable of producing and metabolizing sex steroids. This finding is based on the detection of ste roidogenic enzyme expression as well as the presence of bioactive steroids in both the rodent and human gut. Within the intestinal mucosa, the intestinal epithelial cell layer is one of the main cellular sources of steroids. Glucocorticoid synthesis regulation in the intestinal epithelial cells is unique in that it does not involve the classical positive regulator steroidogenic factor 1 (SF 1) but a closely related homolog, namely the liver receptor homolog 1 (LRH 1). This local production of immunoregulatory glucocorticoids contributes to intestinal homeostasis and has been linked to pathophysiology of inflammatory bowel dis eases. Intestinal epithelial cells also possess the ability to metabolize sex steroids, notably estrogen; this mechanism may impact colorectal cancer development. In this review, we contextualize and discuss what is known about intestinal steroidogenesis and regulation as well as the key role these functions play both in physiological and pathological conditions.

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“…The literature further has established a role for hormones such as thyroxine, cortisol, insulin, EGF, and IGF1, often secreted into colostrum, to influence the transcription, expression, and maturation of these hydrolases (James et al, 1987;Foltzer-Jourdainne et al, 1989;Foltzer-Jourdainne and Raul, 1990;Burrin et al, 2001;Petersen et al, 2002;Lu et al, 2011). These and other studies have demonstrated that several brush border hydrolases are transiently expressed and active in the neonatal colon in addition to the intestine.…”

Section: Downloaded Frommentioning

confidence: 88%

Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

et al. 2018

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A thorough knowledge of the newborn (age, birth to 1 month postpartum) infant's gastrointestinal tract (GIT) is critical to the evaluation of the absorption, distribution, metabolism, and excretion (ADME) of orally administered drugs in this population. Developmental changes in the GIT during the newborn period are important for nutrient uptake as well as the disposition of orally administered medications. Some aspects of gastrointestinal function do not mature until driven by increased dietary complexity and nutritional demands later in the postnatal period. The functionalities present at birth, and subsequent maturation, can also impact the ADME parameters of orally administered compounds. This review will examine some specific contributors to the ADME processes in human neonates, as well as what is currently understood about the drivers for their maturation. Key species differences will be highlighted, with a focus on laboratory animals used in juvenile toxicity studies. Because of the gaps and inconsistencies in our knowledge, we will also highlight areas where additional study is warranted to better inform the appropriate use of medicines specifically intended for neonates.

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Hydrocortisone induces changes in gene expression and differentiation in immature human enterocytes

Cited by 22 publications

References 35 publications

Glucocorticoids regulate barrier function and claudin expression in intestinal epithelial cells via MKP-1

Glucocorticoids regulate barrier function and claudin expression in intestinal epithelial cells via MKP-1

Intestinal steroidogenesis

Physiology of the Neonatal Gastrointestinal System Relevant to the Disposition of Orally Administered Medications

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