Transforming growth factor-β2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine

Nguyen, Duc; Sangild, Per Torp; Østergaard, Morten; Bering, Stine Brandt; Chatterton, Dereck E.W.

doi:10.1152/ajpgi.00193.2014

Cited by 28 publications

(31 citation statements)

References 39 publications

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“…In addition, TGF-β2 specifically attenuates IL1β-induced inflammatory responses in the immature human intestine via an SMAD6- and ERK-dependent mechanism (56). More recently, it has been observed that TGF-β2 and endotoxin interact to regulate homeostasis via IL8 levels in the immature intestine (57). …”

Section: Discussionmentioning

confidence: 99%

What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

et al. 2017

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Human milk provides a very wide range of nutrients and bioactive components, including immune factors, human milk oligosaccharides, and a commensal microbiota. These factors are essential for interconnected processes including immunity programming and the development of a normal infant gastrointestinal microbiome. Newborn immune protection mostly relies on maternal immune factors provided through milk. However, studies dealing with an in-depth profiling of the different immune compounds present in human milk and with the assessment of their natural variation in healthy women from different populations are scarce. In this context, the objective of this work was the detection and quantification of a wide array of immune compounds, including innate immunity factors (IL1β, IL6, IL12, INFγ, TNFα), acquired immunity factors (IL2, IL4, IL10, IL13, IL17), chemokines (IL8, Groα, MCP1, MIP1β), growth factors [IL5, IL7, epidermal growth factor (EGF), granulocyte colony-stimulating factor, granulocyte–macrophage colony-stimulating factor, TGFβ2], and immunoglobulins (IgA, IgG, IgM), in milk produced by healthy women of different ethnicities living in different geographic, dietary, socioeconomic, and environmental settings. Among the analyzed factors, IgA, IgG, IgM, EGF, TGFβ2, IL7, IL8, Groα, and MIP1β were detected in all or most of the samples collected in each population and, therefore, this specific set of compounds might be considered as the “core” soluble immune factors in milk produced by healthy women worldwide. This approach may help define which immune factors are (or are not) common in milk produced by women living in various conditions, and to identify host, lifestyle, and environmental factors that affect the immunological composition of this complex biological fluid.Clinical Trial Registration: , identifier NCT02670278.

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Section: Discussionmentioning

confidence: 99%

What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

et al. 2017

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“…The Th2 cytokines such as IL-4 and IL-13, detected in most of our samples and in higher concentration in colostrum, are anti-inflammatory, down-regulate Toll-like receptor activation in human intestinal epithelial cells (Mueller et al, 2006), and would maintain tolerance during initial bacterial colonization. Similarly, TGF-β1 and TGF-β2 would induce T regulatory cells in mesenteric lymph nodes (Renz et al, 2012) and reduce mucosal levels of inflammatory cytokines (Nguyen et al, 2014; Rautava et al, 2012). …”

Section: Discussionmentioning

confidence: 99%

“…Human milk cytokines like TGF-β2 modulate LPS-induced secretion of pro-inflammatory cytokines (Nguyen et al, 2014) and proliferation and differentiation of lymphocytes, phagocytes, and dendritic cells (Agarwal et al, 2011; Chatterton et al, 2013). In fact, TGF-β family cytokines were detectable in all samples we tested, and at increased concentrations in the mature milk of women delivering VLBW infants, the population with the highest risk of NEC, suggesting highly conserved function and supporting the importance of human milk consumption for premature infants.…”

Section: Discussionmentioning

confidence: 99%

“…IP-10 and chemokines such as IL-8, MCP-1, MIP-1β and IL-17 from the mother’s colostrum may activate the innate immune system against invading pathogens and strengthen the intestinal barrier. In fact, in vitro experiments suggest that, at the levels found in human milk, IL-8 facilitates the maturation of intestinal epithelial cells (Maheshwari et al, 2002; Nguyen et al, 2014). Within the intestinal mucosa, the differentiation of naïve CD4 cells into Th17 cells, which help defend against extracellular pathogens, is modulated by TGFβs concentrations (Chatterton et al, 2013; Galvez, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…It contains the nutrients necessary to promote adequate growth and bioactive substances essential for maturation of the neonatal immune system and intestinal function (Agarwal et al, 2011). Animal and in vitro studies suggest that cytokines may have an important role in the proliferation and migration of intestinal epithelial cells and in modulation of the mucosal immune system (Nguyen et al, 2014; Parigi et al, 2015; Rautava et al, 2012). Their effect could be especially important in low birth weight (LBW) infants (birth weight equal to or below 2500 grams), a population at increased risk of mortality and complications like sepsis or necrotizing enterocolitis (Neu and Walker, 2011; Stoll et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

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Maternal and pregnancy-related factors affecting human milk cytokines among Peruvian mothers bearing low-birth-weight neonates

Zambruni

Villalobos

Somasunderam

et al. 2017

Journal of Reproductive Immunology

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Several cytokines have been detected in human milk but their relative concentrations differ among women and vary over time in the same person. The drivers of such differences have been only partially identified, while the effect of luminal cytokines in the fine-regulation of the intestinal immune system is increasingly appreciated. The aim of this study was to investigate the associations between obstetrical complications and human milk cytokine profiles in a cohort of Peruvian women giving birth to Low Birth Weight (LBW) infants. Colostrum and mature human milk samples were collected from 301 Peruvian women bearing LBW infants. The concentration of twenty-three cytokines was measured using the Luminex platform. Ninety-nine percent of women had at least one identified obstetrical complication leading to intra-uterine growth restriction and/or preterm birth. Median weight at birth was 1,420 grams; median gestational age 31 weeks. A core of 12 cytokines, mainly involved in innate immunity and epithelial cell integrity, was detectable in most samples. Maternal age, maternal infection, hypertensive disorders, preterm labor, and premature rupture of membranes were associated with specific cytokine profiles both in colostrum and mature human milk. Mothers of Very LBW (VLBW) neonates had significantly higher concentrations of chemokines and growth factor cytokines both in their colostrum and mature milk compared with mothers of larger neonates. Thus, maternal conditions affecting pregnancy duration and in utero growth are also associated with specific human milk cytokine signatures.

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Cytokines in milk and the role of TGF-beta

Brenmoehl

Ohde

Wirthgen

et al. 2018

Best Practice & Research Clinical Endocrinology & Metab

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Cytokines are required for normal growth and development of the mammary gland and TGF-β prominently represents an established effector of apoptosis, e.g., during involution of the mammary gland. By the control of intracellular signaling pathways, including JAK/STAT, MAPK, PI-3K, and NF-κB, cytokines efficiently regulate cell proliferation and inflammation in the breast. Therefore, cytokines are discussed also in a context of malignant mammary growth. As a group of tissue hormones produced by somatic cells or by cells from the immune system, cytokines are defined by their immunomodulatory potential. Over the past 40 years, multiple cytokines were identified in colostrum and milk. Importantly, cytokines derived from mammary secretions after birth are required for maturation of the immune system in the developing gastrointestinal tract from the suckling. Moreover, recent studies have further assessed the particular interactions between probiotic bacterial strains and cytokines. In light of the increasing prevalence of inflammatory diseases of the gastrointestinal system, the effects of probiotic microorganisms during milk fermentation may have immunotherapeutic potential in the future.

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Transforming growth factor-β2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine

Abstract: Nguyen DN, Sangild PT, Østergaard MV, Bering SB, Chatterton DE. Transforming growth factor-␤2 and endotoxin interact to regulate homeostasis via interleukin-8 levels in the immature intestine.

Cited by 28 publications

References 39 publications

What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

What’s Normal? Immune Profiling of Human Milk from Healthy Women Living in Different Geographical and Socioeconomic Settings

Maternal and pregnancy-related factors affecting human milk cytokines among Peruvian mothers bearing low-birth-weight neonates

Cytokines in milk and the role of TGF-beta

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