An easy way to solve two-loop vertex integrals

Negative dimensional integration is a step further dimensional regularization ideas. In this approach, based on the principle of analytic continuation, Feynman integrals are polynomial ones and for this reason very simple to handle, contrary to the usual parametric ones. The result of the integral worked out in $D<0$ must be analytically continued again --- of course --- to real physical world, $D>0$, and this step presents no difficulties. We consider four two-loop three-point vertex diagrams with arbitrary exponents of propagators and dimension. These original results give the correct well-known particular cases where the exponents of propagators are equal to unity.Comment: 13 pages, LaTeX, 4 figures, misprints correcte

Vectorial secretion of interleukin-8 mediates autocrine signalling in intestinal epithelial cells via apically located CXCR1

BackgroundIn the intestinal mucosa, several adaptations of TLR signalling have evolved to avoid chronic inflammatory responses to the presence of commensal microbes. Here we investigated whether polarized monolayers of intestinal epithelial cells might regulate inflammatory responses by secreting IL-8 in a vectorial fashion (i.e. apical versus basolateral) depending on the location of the TLR stimulus.ResultsIn the Caco-2 BBE model of polarized villus-like epithelium, apical stimulation with TLR2 and TLR5 ligands resulted in the apical secretion of IL-8. The CXCR1 receptor for IL-8 was expressed only on the apical membrane of Caco-2 BBE cells and differentiated epithelial cells in the human small intestine and colon. Transcriptome analyses revealed that Caco-2 BBE cells respond to stimulation with IL-8 supporting the hypothesis that IL-8 induces G protein-coupled receptor signalling.ConclusionsThese results show that IL-8 induces autocrine signalling via an apical CXCR1 in Caco-2 BBE intestinal epithelial cells and that this receptor is also expressed on the apical surface of differentiated human intestinal epithelial cells in vivo, suggesting an autocrine function for IL-8 secreted in the lumen

Mechanisms underlying the skin-gut cross talk in the development of ige-mediated food allergy

Immune-globulin E (IgE)-mediated food allergy is characterized by a variety of clinical entities within the gastrointestinal tract, skin and lungs, and systemically as anaphylaxis. The default response to food antigens, which is antigen specific immune tolerance, requires exposure to the antigen and is already initiated during pregnancy. After birth, tolerance is mostly acquired in the gut after oral ingestion of dietary proteins, whilst exposure to these same proteins via the skin, especially when it is inflamed and has a disrupted barrier, can lead to allergic sensitization. The crosstalk between the skin and the gut, which is involved in the induction of food allergy, is still incompletely understood. In this review, we will focus on mechanisms underlying allergic sensitization (to food antigens) via the skin, leading to gastrointestinal inflammation, and the development of IgE-mediated food allergy. Better understanding of these processes will eventually help to develop new preventive and therapeutic strategies in children

Immunological effects of human milk oligosaccharides

Human milk oligosaccharides (HMOs) comprise a group of structurally complex, unconjugated glycans that are highly abundant in human milk. HMOs are minimally digested in the gastrointestinal tract and reach the colon intact, where they shape the microbiota. A small fraction of HMOs is absorbed, reaches the systemic circulation, and is excreted in urine. HMOs can bind to cell surface receptors expressed on epithelial cells and cells of the immune system and thus modulate neonatal immunity in the infant gut, and possibly also sites throughout the body. In addition, they have been shown to act as soluble decoy receptors to block the attachment of various microbial pathogens to cells. This review summarizes the current knowledge of the effects HMOs can have on infections, allergies, auto-immune diseases and inflammation, and will focus on the role of HMOs in altering immune responses through binding to immune-related receptors.</p

Immunological effects of human milk oligosaccharides

Human milk oligosaccharides (HMOs) comprise a group of structurally complex, unconjugated glycans that are highly abundant in human milk. HMOs are minimally digested in the gastrointestinal tract and reach the colon intact, where they shape the microbiota. A small fraction of HMOs is absorbed, reaches the systemic circulation, and is excreted in urine. HMOs can bind to cell surface receptors expressed on epithelial cells and cells of the immune system and thus modulate neonatal immunity in the infant gut, and possibly also sites throughout the body. In addition, they have been shown to act as soluble decoy receptors to block the attachment of various microbial pathogens to cells. This review summarizes the current knowledge of the effects HMOs can have on infections, allergies, auto-immune diseases and inflammation, and will focus on the role of HMOs in altering immune responses through binding to immune-related receptors.</p

Late rather than early responses of human dendritic cells highlight selective induction of cytokines, chemokines and growth factors by probiotic bacteria.

The probiotic properties of commensal bacteria including lactobacilli and bifidobacteria are likely to be determined at least in part by their effects on dendritic cells. Like traditional immune stimulants such as lipopolysaccharides (LPS), probiotic bacteria promote maturation of cultured human dendritic cells (DC) by inducing elevated expression of MHC-II and co-stimulatory molecules. Different effects have been reported on cytokine induction, especially of major regulatory cytokines such as TNF-a, IL-12 and IL-10. Yet, these previous analyses have failed to reveal consistent differences between such effects of probiotics on the one hand, and of LPS on the other. Selective response markers for probiotics, however, would be important for our understanding of their biological properties and for a rational selection of strains for in vivo studies. In this study, we compared in detail both early and late effects on cultured human DC of 4 different probiotics with those of LPS. At the early stages of stimulation, all stimuli induced qualitatively very similar responses in DC at the level of surface markers and secretion of cytokines and chemokines. A lower immune stimulatory effect was observed by Bifidobacterium animalis BB-12 as compared to lactobacilli. Late responses, on the other hand, tended to diverge. Microarray transcript profiling for 268 cytokines, chemokines, growth factors and their receptors after 2 days of culture revealed various transcripts to be selectively induced by certain probiotics but not LPS. Our data indicate that late rather than early DC responses may be helpful to clarify the divergent biological effects of probiotics on human innate immune responses

Induction of human tolerogenic dendritic cells by 3′-sialyllactose via TLR4 is explained by LPS contamination

The human milk oligosaccharide 3′-sialyllactose (3′SL) has previously been shown to activate murine dendritic cells (DC) in a Toll-like receptor (TLR) 4-mediated manner ex vivo. In this study we aimed to investigate whether 3′SL has similar immunomodulatory properties on human DC. 3′SL was shown to induce NF-κB activation via human TLR4. However, LPS was detected in the commercially obtained 3′SL from different suppliers. After the removal of LPS from 3′SL, we studied its ability to modify DC differentiation in vitro. In contrast to LPS and 3′SL, LPS-free 3′SL did not induce functional and phenotypical changes on immature DC (iDC). iDC that were differentiated in the presence of LPS or 3′SL showed a semi-mature phenotype (i.e., fewer CD83+CD86+ DC), produced IL-10 and abrogated IL-12p70 and tumor necrosis factor-alpha levels upon stimulation with several TLR ligands. Differentiation into these tolerogenic DC was completely abrogated by LPS removal from 3′SL. In contrast to previous reports in mice, we found that LPS-free 3′SL does not activate NF-κB via human TLR4. In conclusion, removing LPS from (oligo)saccharide preparations is necessary to study their potential immunomodulatory function

Bovine Milk-Derived Extracellular Vesicles Inhibit Catabolic and Inflammatory Processes in Cartilage from Osteoarthritis Patients

SCOPE: Data from the Osteoarthritis Initiative shows that females who drink milk regularly have less joint cartilage loss and OA progression, but the biologic mechanism is unclear. Bovine milk is a rich source of extracellular vesicles (EVs), which are small phospholipid bilayer bound structures that facilitate intercellular communication. In this study, the authors aim to evaluate whether these EVs may have the capacity to protect cartilage from osteoarthritis patients, ex vivo, by directly effecting chondrocytes. METHODS AND RESULTS: Human cartilage explants are exposed to cow's milk-derived EVs (CMEVs), which results in reduced sulfated glycosaminoglycan release and inhibition of metalloproteinase-1 expression. Incubation of articular chondrocytes with CMEVs also effectively reduces expression of cartilage destructive enzymes (ADAMTS5, MMPs), which play key roles in the disease progression. In part, these findings are attributed to the presence of TGFβ on these vesicles, and in addition, a possible role is reserved for miR-148a, which is functionally transferred by CMEVs. CONCLUSION: These findings highlight the therapeutic potential of local CMEV delivery in osteoarthritic joints, where inflammatory and catabolic mediators are responsible for joint pathology. CMEVs are carriers of both TGFβ and miR-148a, two essential regulators for maintaining chondrocyte homeostasis and protection against cartilage destruction

Flood Control: How Milk-Derived Extracellular Vesicles Can Help to Improve the Intestinal Barrier Function and Break the Gut-Joint Axis in Rheumatoid Arthritis

Many studies provided compelling evidence that extracellular vesicles (EVs) are involved in the regulation of the immune response, acting as both enhancers and dampeners of the immune system, depending on the source and type of vesicle. Research, including ours, has shown anti-inflammatory effects of milk-derived EVs, using human breast milk as well as bovine colostrum and store-bought pasteurized cow milk, in in vitro systems as well as therapeutically in animal models. Although it is not completely elucidated which proteins and miRNAs within the milk-derived EVs contribute to these immunosuppressive capacities, one proposed mechanism of action of the EVs is via the modulation of the crosstalk between the (intestinal) microbiome and their host health. There is increasing awareness that the gut plays an important role in many inflammatory diseases. Enhanced intestinal leakiness, dysbiosis of the gut microbiome, and bowel inflammation are not only associated with intestinal diseases like colitis and Crohn's disease, but also characteristic for systemic inflammatory diseases such as lupus, multiple sclerosis, and rheumatoid arthritis (RA). Strategies to target the gut, and especially its microbiome, are under investigation and hold a promise as a therapeutic intervention for these diseases. The use of milk-derived EVs, either as stand-alone drug or as a drug carrier, is often suggested in recent years. Several research groups have studied the tolerance and safety of using milk-derived EVs in animal models. Due to its composition, milk-derived EVs are highly biocompatible and have limited immunogenicity even cross species. Furthermore, it has been demonstrated that milk-derived EVs, when taken up in the gastro-intestinal tract, stay intact after absorption, indicating excellent stability. These characteristics make milk-derived EVs very suitable as drug carriers, but also by themselves, these EVs already have a substantial immunoregulatory function, and even without loading, these vesicles can act as therapeutics. In this review, we will address the immunomodulating capacity of milk-derived EVs and discuss their potential as therapy for RA patients. REVIEW CRITERIA: The search terms "extracellular vesicles", "exosomes", "microvesicles", "rheumatoid arthritis", "gut-joint axis", "milk", and "experimental arthritis" were used. English-language full text papers (published between 1980 and 2021) were identified from PubMed and Google Scholar databases. The reference list for each paper was further searched to identify additional relevant articles