scholarly journals Sex Hormones and Aging Modulate Interferon Lambda 1 Production and Signaling by Human Uterine Epithelial Cells and Fibroblasts

2021 ◽  
Vol 12 ◽  
Author(s):  
Mickey V. Patel ◽  
Daniel C. Hopkins ◽  
Fiona D. Barr ◽  
Charles R. Wira
Keyword(s):  
Epithelial Cells ◽  
Menopausal Status ◽  
Immune Defense ◽  
Poly I:C ◽  
Stromal Fibroblast ◽  
Cell Type ◽  
Uterine Epithelial Cells ◽  
Uterine Endometrium ◽  
Human Uterine Endometrium ◽  
Stimulation Of

Estradiol (E2) and progesterone (P) have potent effects on immune function in the human uterine endometrium which is essential for creating an environment conducive for successful reproduction. Type III/lambda (λ) interferons (IFN) are implicated in immune defense of the placenta against viral pathogens, which occurs against the backdrop of high E2 and P levels. However, the effect of E2 and P in modulating the expression and function of IFNλ1 in the non-pregnant human uterine endometrium is unknown. We generated purified in vitro cultures of human uterine epithelial cells and stromal fibroblast cells recovered from hysterectomy specimens. Poly (I:C), a viral dsRNA mimic, potently increased secretion of IFNλ1 by both epithelial cells and fibroblasts. The secretion of IFNλ1 by epithelial cells significantly increased with increasing age following poly (I:C) stimulation. Stimulation of either cell type with E2 (5x10-8M) or P (1x10-7M) had no effect on expression or secretion of IFNλ1 either alone or in the presence of poly (I:C). E2 suppressed the IFNλ1-induced upregulation of the antiviral IFN-stimulated genes (ISGs) MxA, OAS2 and ISG15 in epithelial cells, but not fibroblasts. Estrogen receptor alpha (ERα) blockade using Raloxifene indicated that E2 mediated its inhibitory effects on ISG expression via ERα. In contrast to E2, P potentiated the upregulation of ISG15 in response to IFNλ1 but had no effect on MxA and OAS2 in epithelial cells. Our results demonstrate that the effects of E2 and P on IFNλ1-induced ISGs are cell-type specific. E2-mediated suppression, and selective P-mediated stimulation, of IFNλ1-induced ISG expression in uterine epithelial cells suggest that the effects of IFNλ1 varies with menstrual cycle stage, pregnancy, and menopausal status. The suppressive effect of E2 could be a potential mechanism by which ascending pathogens from the lower reproductive tract can infect the pregnant and non-pregnant endometrium.

Dopaminergic stimulation of cAMP accumulation in cultured rat mesangial cells

1987 ◽  
Vol 253 (2) ◽  
pp. H358-H364 ◽  
Author(s):  
P. J. Shultz ◽  
J. R. Sedor ◽  
H. E. Abboud
Keyword(s):  
Epithelial Cells ◽  
Mesangial Cells ◽  
Sch 23390 ◽  
Type I ◽  
Camp Accumulation ◽  
Cell Type ◽  
Glomerular Cell ◽  
Da Receptors ◽  
Dopaminergic Stimulation ◽  
Stimulation Of

Dopamine (DA) alters renal hemodynamics, and DA receptors have been demonstrated in isolated glomeruli. To determine the glomerular cell type bearing DA receptors, we studied the effect of dopaminergic agonists and antagonists on adenosine 3',5'-cyclic monophosphate (cAMP) accumulation in rat glomerular mesangial and epithelial cells in culture. DA caused a marked dose- and time-dependent increase in cAMP accumulation in mesangial but not epithelial cells. The stimulatory effect of DA was abolished by the DA antagonists haloperidol, trifluoperazine, and cis-thiothixene but not by beta- or alpha-adrenergic or histamine antagonists. Similar to the effects of DA, two dopamine type I receptor agonists, fenoldopam and SKF 38393, markedly stimulated cAMP accumulation in the mesangial cells. Moreover, the effects of DA were blocked by Sch 23390, a specific DA1 receptor antagonist, but not domperidone, a specific DA2 antagonist. These results show that DA regulates cAMP accumulation in mesangial cells via DA1-type receptors.

EFFECT OF OESTRADIOL ON THE POST-PARTUM RAT UTERUS: PEROXIDASE ACTIVITY AND COLLAGEN BREAKDOWN

1980 ◽  
Vol 85 (3) ◽  
pp. 387-391 ◽  
Author(s):  
J. F. WOESSNER ◽  
JANET N. RYAN
Keyword(s):  
Epithelial Cells ◽  
Peroxidase Activity ◽  
Post Partum ◽  
Cell Type ◽  
Rat Uterus ◽  
Uterine Epithelial Cells ◽  
Uterine Involution ◽  
Tenfold Increase

Treatment of parturient rats with 100 μg oestradiol/day caused a significant retardation of uterine involution and collagen breakdown. The post-partum uterus had a peroxidase activity of 180 μmol H2O2 reduced/min per uterus. Treatment with oestradiol caused an eight- to tenfold increase in this activity within 3–4 days. Treatment of rats with 4 mg cortisol/day commencing 3 days prepartum had no effect on uterine peroxidase activity but it blocked the oestradiol-induced increase in peroxidase. Cortisol had no effect on collagen breakdown and did not reverse the inhibition of collagen breakdown produced by oestradiol. It is postulated that the effects of oestradiol on peroxidase activity are mediated by uterine epithelial cells but that oestradiol effects on collagen breakdown may be mediated by another cell type.

scholarly journals Stimulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase in mouse uterine epithelial cells by oestradiol-17 β

1984 ◽  
Vol 218 (3) ◽  
pp. 849-855 ◽  
Author(s):  
P A Wilce ◽  
L Leijten ◽  
L Martin
Keyword(s):  
Cell Cycle ◽  
Enzyme Activity ◽  
Epithelial Cells ◽  
Time Course ◽  
Hormone Treatment ◽  
S Phase ◽  
Uterine Epithelial Cells ◽  
Coa Reductase ◽  
Two Peaks ◽  
Stimulation Of

The characteristics of 3-hydroxy-3-methylglutaryl-CoA reductase from mouse uterine epithelial cells were studied. Preliminary experiments showed that enzyme activity was stimulated approx. 10-fold 18h after administration of 100ng of oestradiol-17 beta. This activity was associated with all particulate fractions of the uterine luminal cell. The Km for D-3-hydroxy-3-methylglutaryl-CoA was 5.54 +/- 1.12 microM. The detailed time-course of oestrogen stimulation showed two peaks of activity, 9 and 15h after hormone treatment. The DNA content of the epithelial cells doubled between 6 and 12h after hormone treatment, whereas the protein content increased linearly over the 18h period. The peak of enzyme activity at 9h is associated with early S phase of the epithelial cells; the peak at 15h may be associated with a second S phase or with mitosis. Pretreatment with progesterone for 3 days before injection of oestradiol-17 beta (a treatment which inhibits uterine epithelial DNA synthesis) reduced the oestrogenic stimulation of enzyme activity by 63%; progesterone treatment alone did not stimulate enzyme activity. These data suggest that uterine epithelial 3-hydroxy-3-methylglutaryl-CoA reductase may play an important role in the cell cycle in this tissue.

scholarly journals TLR3-mediated NF-κB signaling in human esophageal epithelial cells

2009 ◽  
Vol 297 (6) ◽  
pp. G1172-G1180 ◽  
Author(s):  
Diana M. Lim ◽  
Sneha Narasimhan ◽  
Carmen Z. Michaylira ◽  
Mei-Lun Wang
Keyword(s):  
Immune Response ◽  
Epithelial Cells ◽  
Inflammatory Response ◽  
Innate Immune Response ◽  
Innate Immune ◽  
Poly I:C ◽  
Esophageal Epithelium ◽  
Esophageal Epithelial Cells ◽  
Stimulation Of

Despite its position at the front line against ingested pathogens, very little is presently known about the role of the esophageal epithelium in host innate immune defense. As a key player in the innate immune response, Toll-like receptor (TLR) signaling has not been well characterized in human esophageal epithelial cells. In the present study, we investigated the inflammatory response and signaling pathways activated by TLR stimulation of human esophageal cells in vitro. Using quantitative RT-PCR, we profiled the expression pattern of human TLRs 1–10 in primary esophageal keratinocytes (EPC2), immortalized nontransformed esophageal keratinocytes (EPC2-hTERT), and normal human esophageal mucosal biopsies and found that TLRs 1, 2, 3, and 5 were expressed both in vivo and in vitro. Using the cytokine IL-8 as a physiological read out of the inflammatory response, we found that TLR3 is the most functional of the expressed TLRs in both primary and immortalized esophageal epithelial cell lines in response to its synthetic ligand polyinosinic polycytidylic acid [poly(I:C)]. Through reporter gene studies, we show that poly(I:C)-induced NF-κB activation is critical for the transactivation of the IL-8 promoter in vitro and that nuclear translocation of NF-κB occurs at an early time point following poly(I:C) stimulation of esophageal epithelial cells. Importantly, we also show that poly(I:C) stimulation induces the NF-κB-dependent esophageal epithelial expression of TLR2, leading to enhanced epithelial responsiveness of EPC2-hTERT cells to TLR2 ligand stimulation, suggesting an important regulatory role for TLR3-mediated NF-κB signaling in the innate immune response of esophageal epithelial cells. Our findings demonstrate for the first time that TLR3 is highly functional in the human esophageal epithelium and that TLR3-mediated NF-κB signaling may play an important regulatory role in esophageal epithelial homeostasis.

scholarly journals S127 Influenza A and Poly(I:C) Induce α Vβ6-Integrin-Mediated TGFβ Activity in Human Epithelial Cells Via Stimulation of TLR3

Thorax ◽  
2012 ◽  
Vol 67 (Suppl 2) ◽  
pp. A61.1-A61
Author(s):  
L Jolly ◽  
A Stavrou ◽  
S Violette ◽  
P Weinreb ◽  
T Hussell ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Influenza A ◽  
Poly I:C ◽  
Human Epithelial Cells ◽  
Stimulation Of

scholarly journals Stimulation of GPR30 Increases Release of EMMPRIN-Containing Microvesicles in Human Uterine Epithelial Cells

2012 ◽  
Vol 97 (12) ◽  
pp. 4613-4622 ◽  
Author(s):  
Lindsey A. Burnett ◽  
Mallory M. Light ◽  
Pavni Mehrotra ◽  
Romana A. Nowak
Keyword(s):  
Epithelial Cells ◽  
Uterine Epithelial Cells ◽  
Stimulation Of
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