Trefoil factor 3 (TFF3) from human breast milk activates PAR-2 receptors, of the intestinal epithelial cells HT-29, regulating cytokines and defensins

Barrera, Girolamo Jose; Tortolero, G. Sanchez

doi:10.4149/bll_2016_066

Cited by 14 publications

(19 citation statements)

References 12 publications

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“…Generally, this molecule improves healing in the GI tract. The TFF3 present in breast milk produces downregulation of cytokines and promotes hBDs expression in IECs (71). Glucagon-like peptide 1 (GLP-1) is secreted from the enteroendocrine cell in the distal intestine and plays a role in regulating glucose metabolism and food intake.…”

Section: Anti-inflammatory Factors and Effectsmentioning

confidence: 99%

Innate Immunity and Breast Milk

2017

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Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant’s optimal growth and development. The growing infant’s immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant’s innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk’s effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant’s intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant’s gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant.

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Section: Anti-inflammatory Factors and Effectsmentioning

confidence: 99%

Innate Immunity and Breast Milk

2017

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“…Thus, to some extent, the TFF2-CXR4 axis in particular seems to play a direct role in gastric repair [ 92 ], as well as in suppressing colorectal carcinogesis via the neural innervation of splenic memory T-cells [ 24 ]. Furthermore, cell migration was also promoted by TFF2 (2 × 10 −7 M) via the activation of the proteinase-activated receptor PAR4 [ 93 ], and TFF3 (10 −6 M) was claimed to activate PAR2 [ 94 ].…”

Section: Introductionmentioning

confidence: 99%

Trefoil Factor Family (TFF) Peptides and Their Diverse Molecular Functions in Mucus Barrier Protection and More: Changing the Paradigm

Hoffmann

2020

IJMS

142

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Trefoil factor family peptides (TFF1, TFF2, TFF3) are typically co-secreted together with mucins. Tff1 represents a gastric tumor suppressor gene in mice. TFFs are also synthesized in minute amounts in the immune and central nervous systems. In mucous epithelia, they support rapid repair by enhancing cell migration (“restitution”) via their weak chemotactic and anti-apoptotic effects. For a long time, as a paradigm, this was considered as their major biological function. Within recent years, the formation of disulfide-linked heterodimers was documented for TFF1 and TFF3, e.g., with gastrokine-2 and IgG Fc binding protein (FCGBP). Furthermore, lectin activities were recognized as enabling binding to a lipopolysaccharide of Helicobacter pylori (TFF1, TFF3) or to a carbohydrate moiety of the mucin MUC6 (TFF2). Only recently, gastric TFF1 was demonstrated to occur predominantly in monomeric forms with an unusual free thiol group. Thus, a new picture emerged, pointing to diverse molecular functions for TFFs. Monomeric TFF1 might protect the gastric mucosa as a scavenger for extracellular reactive oxygen/nitrogen species. Whereas, the TFF2/MUC6 complex stabilizes the inner layer of the gastric mucus. In contrast, the TFF3–FCGBP heterodimer (and also TFF1–FCGBP) are likely part of the innate immune defense of mucous epithelia, preventing the infiltration of microorganisms.

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“…Alterações na região codificadora do gene TFF3 podem interferir em suas funções e padrões de interação proteica, de modo a aumentar a suscetibilidade de pacientes à endometriose. O TFF3 interage e regula o receptor ativado por protease 2 (PAR-2) (BARRERA; TORTOLERO, 2016). O PAR-2 está relacionado a respostas inflamatórias, excesso de peso (LIM et al, 2013), metabolismo (BADEANLOU et al, 2011) e responde a enzimas proteolíticas de microrganismos (BADEANLOU et al, 2011, p. 2).…”

Section: Polimorfismos Genéticos Na Endometrioseunclassified