Cotreatment With Interleukin 4 and Interleukin 10 Modulates Immune Cells and Prevents Hypertension in Pregnant Mice

Chatterjee, Piyali; Chiasson, Valorie L; Seerangan, Geetha; Tobin, Richard P.; Kopriva, Shelley; Newell‐Rogers, M. Karen

doi:10.1093/ajh/hpu100

Cited by 58 publications

(35 citation statements)

References 41 publications

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“…Our findings are consistent with our hypothesis that IL10 expression is decreased in maternal food-restricted placentas. These findings are in line with human data showing that placental insufficiency uniformly seen in various disorders of pregnancy such as recurrent miscarriages, preeclampsia, and/or intrauterine growth restriction may be due to disordered immune tolerance and/or dysregulation of IL10 [11,21-23]. …”

Section: Discussionsupporting

confidence: 89%

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Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Chu¹,

Thamotharan²,

Ganguly³

et al. 2016

Nutrition Research

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Intrauterine growth restriction (IUGR) affects up to 10% of pregnancies and often results in short- and long- term sequelae for offspring. The mechanisms underlying IUGR are poorly understood, but it is known that healthy placentation is essential for nutrient provision to fuel fetal growth, and is regulated by immunologic inputs. We hypothesized that in pregnancy, maternal food restriction (FR) resulting in IUGR would decrease the overall immunotolerant milieu in the placenta, leading to increased cellular stress and death. Our specific objectives were to evaluate: (1) key cytokines (e.g. IL10) that regulate maternal-fetal tolerance, (2) cellular processes (autophagy and ER stress) that are immunologically-mediated and important for cellular survival and functioning, and (3) evaluate the resulting IUGR phenotype and placental histopathology. After subjecting pregnant mice to mild and moderate FR from gestational day (GD) 10 to 19, we collected placentas and embryos at GD19. We examined RNA sequencing data to identify immunologic pathways affected in IUGR-associated placentas and validated mRNA expression changes of genes important in cellular integrity. We also evaluated histopathologic changes in vascular and trophoblastic structures as well as protein expression changes in autophagy, ER stress, and apoptosis in the mouse placentas. Several differentially expressed genes were identified in FR compared to control mice, including a considerable subset that regulates immune tolerance, inflammation and cellular integrity. In summary, maternal food restriction decreases anti-inflammatory effect of IL10 and suppresses placental autophagic and ER stress responses, despite evidence of dysregulated vascular and trophoblast structures leading to IUGR.

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Section: Discussionsupporting

confidence: 89%

“…Lastly, the protective effects of IL10 on vascular function and inflammation have been observed both in pregnancy models and non- pregnancy states [22-23]. IL10 knockout mice have been shown to exhibit impaired spiral artery remodeling and poor placental angiogenesis, resulting in IUGR, when exposed to environmental toxins.…”

Section: Discussionmentioning

confidence: 99%

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Chu¹,

Thamotharan²,

Ganguly³

et al. 2016

Nutrition Research

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“…Dicky et al found that anti-IL-4 treatment resulted in a decrease in blood pressure in hypertensive NZBNZWF1 mice, suggesting a role of IL-4 in promoting blood pressure [28]. In contrast, Chatterjee et al found that treatment with exogenous IL-4 significantly decreased blood pressure in P-PIC mice, which is a model of pregnancy-induced hypertension syndrome, indicating a protective role of IL-4 in hypertension [29]. Taken together, these studies suggested a complex role of the Th2 response in hypertension.…”

Section: Discussionmentioning

confidence: 99%

Circulating Th1, Th2, and Th17 Levels in Hypertensive Patients

Cheng

et al. 2017

Disease Markers

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Background Evidence from experimental studies showed that Th1, Th2, and Th17 play a pivotal role in hypertension and target organ damage. However, whether changes in the circulating Th1, Th2, and Th17 levels are associated with nondipper hypertension and carotid atherosclerotic plaque in hypertension has yet to be investigated. Methods Th1, Th2, and Th17 levels were detected using a flow cytometric analysis, and their related cytokines were measured by enzyme-linked immunosorbent assay in 45 hypertensive patients and 15 normotensive subjects. Results The frequencies of Th1 and Th17 in hypertensive patients, especially in nondipper patients and patients with carotid atherosclerotic plaque, were markedly higher than those in the control group; this was accompanied by higher IFN-γ and IL-17 levels. In contrast, the Th2 frequencies and IL-4 levels in hypertensive patients, especially in nondipper patients and patients with carotid atherosclerotic plaque, were significantly lower than those in the control group. Conclusions The changes in Th1, Th2, and Th17 activity are associated with the onset of the nondipper type and carotid atherosclerotic plaque in hypertensive patients.

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“…However, TLR3, TLR7, and TLR8 have all been associated with maternal hypertension in rodent models with preeclampsia-like symptoms (Tinsley et al, 2009;Chatterjee et al, 2011Chatterjee et al, , 2012Chatterjee et al, , 2013Chatterjee et al, , 2015Ishimoto et al, 2013;Kopriva et al, 2013). Moreover TLR7/8, as well as TLR9, from SHR splenocytes evoked the greatest proinflammatory responses to angiotensin II when primed with their respective exogenous ligands (Harwani et al, 2012).…”

Section: B Hypertensionmentioning

confidence: 99%

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

2015

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Cotreatment With Interleukin 4 and Interleukin 10 Modulates Immune Cells and Prevents Hypertension in Pregnant Mice

Abstract: Taken together, these data demonstrate that exogenous IL-4 and IL-10 administration concurrently during pregnancy can normalize immune cell subsets and prevent PE induced by maternal immune system activation.

Cited by 58 publications

References 41 publications

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Gestational food restriction decreases placental interleukin-10 expression and markers of autophagy and endoplasmic reticulum stress in murine intrauterine growth restriction

Circulating Th1, Th2, and Th17 Levels in Hypertensive Patients

Toll-like Receptors in the Vascular System: Sensing the Dangers Within

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