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BACKGROUND It has been reported that boron induces changes in the immune response, including in inflammatory processes. Recently, the effect of boric acid has been documented on the differentiation of lymphocyte clusters in mice and rats. However, the differences among boron-containing compounds (BCC) have been poorly explored. METHODS In this study, we analyzed the effects after oral administration of boric acid (BOR), methylboronic (MET), 3-thyenylboronic (3TB), 4-hydroxymethyl-phenylboronic (4 M P) and 4-methanesulfonyl-phenylboronic (4SP) acids on the populations of lymphocytes from spleen and Peyer’s patch (PP) as well as on antibodies. Groups of six male BALB/C were orally treated with 4.6 mg/kg of body weight with BOR, MET, 3TB, 4 M P, and 4SP/daily for 10 days) or vehicle (VEH) as a control group. After euthanasia, the spleen and small intestine were dissected. We conducted flow cytometry assays to assess B, CD3+ T, CD4+ T, and CD8+ T cells. Levels of IgG and IgM in serum, and IgA in intestinal fluid samples were analyzed by enzyme immunoassay. RESULTS In particular, we observed the effects of the administration of boronic acids on the number of lymphocytes; these changes were more notable in spleen than in PP. We found different profiles for each boron-containing compound, that is BOR induced an increase in the percentage of CD8+ T and CD19+/IgA+ cells in spleen, but a decrease in CD8+ T and B220+/CD19+ cells in PP. Meanwhile MET induced a decrease of CD4+ T in spleen, but induced an increase of CD4+ T cells and a decrease in the number of CD8+ T cells in PP. Boronic acids with an aromatic ring moiety induced changes in serum immunoglobulins levels, while 3TB acid induced a notable increase in S-IgA. CONCLUSIONS Effects in lymphocyte populations and antibodies are different for each tested compound. These results highlight the establishment of the necessary structure-activity relationship for BCC as immunomodulatory drugs. This is relevant in the biomedical field due to their attractiveness for selecting compounds to develop therapeutic tools.

GPR41 and GPR43 receptors are located at the level of the ileum and colon in the enteroendocrine cells, being activated by short-chain bacterial fatty acids, products of fermentation, these become a key to activate the mechanisms involved in this intestinal homeostasis. GPR43 and GPR41 mediate inflammatory processes such as colitis, but it has not been demonstrated their participation in vivo models of stress. In a model of acute and chronic restraint stress BALB/c mice we evaluated their expression. The measurement of serum corticosterone was performed to validate our model. Gene expression of Gpr41/Gpr43 through qPCR and protein expression of GPR41/GPR43 by Western Blot in both Large Intestine (IG) and Small Intestine (ID). Our results show that stress increases corticosterone levels being higher in chronic stress. Gene expression may show an increase for both receptors in chronic stress. Protein expression, unlike gene, has a greater increase in acute stress, except for GPR41 in ID where its increase is not significant. This suggests that an acute stimulation increases the expression of this receptor to conserve intestinal homeostasis, which initially deplete the gene machinery and then increase it by the constant appearance of the stressor stimulus although there seem to be post-translational mechanisms that do not allow. This shows us that the gradual increase of corticosterone apparently affects the expression of the protein of both receptors.

Nervous System in coordination with an other systems as endocrine and immune. Several studies have shown that conditions of stress modify the expression and concentration of SIgA, which has been attributed to factors as glucocorticoids and catecholamines produced in the adrenal gland. The objective of this study was determined the effect of adrenalectomy on secretion of IgA in the large intestine of BALB/c mice under acute stress by immobilization. We determined the concentration of serum corticosterone by RIA, the concentration of SIgA in intestinal fluid by ELISA and the percentage of T CD4+, T CD8+, B lymphocytes and plasma cells IgA+ in lamina propria by flow cytometry. The results showed that the serum corticosterone in the group SHAM+stress increased due to the effect of the activation of the hypothalamic-pituitary-adrenal axis and the concentration of SIgA. Regarding the cellular percentage, we founded an increased percentage of lymphocytes B and plasma cells positives to IgA; due to the effect of glucocorticoids and catecholamines over the cells of the immune system. The concentration of SIgA in intestinal fluid decreased compared to the SHAM group. Stress showed an important decreased on SIgA levels in comparison with SHAM+E group. We can conclude that the suppression of cortisol and catecholamines with acute exposure to stress directly affects the immune status in the large intestine. This work was supported by SIP-COFAA-IPN .

To maintain internal balance is a complex process that requires the activation of neuroendocrine mechanisms that allows organisms to conserve the systemic, tissular and cellular homeostasis. One of the most important pathways of the immune regulation in gut is through the Acetylcholine (ACh) release, which not only modules inflammation by suppressing the release of pro-inflammatory cytokines (cholinergic anti-inflammatory pathway); but also modulates IgA secretion by muscarinic receptors, in accordance with studies made in small and large intestine. As the last response has been poorly studied in animal models, we made a truncal vagotomy in BALB/c mice in order to know if vagus nerve module the IgA secretion. Twenty male mice underwent sham or sub-diaphragmatic truncal vagotomy, on 14th postoperative day were collected plasma, lymphocytes of Peyer’s patches and lamina propria and intestinal fluid in order to determine total secretory IgA by ELISA, plasmatic cells IgA+ and intracellular cytokines (TGF-b, IL-4, IL-5, IL-6, IL-10) by flow cytometry. The vagotomy group showed a decrease in levels of SIgA in intestinal fluid and TGF-b, IL-4, IL-5, IL-6 and IL-10 compared with SHAM group. Moreover, further studies are needed to clarify whether the changes in small intestine IgA and cytokine levels are induced by vagotomy directly or produced by some other indirect effects. This work was supported by SIP-COFAA-IPN .

Stress, which has become a public health problem, is an emotional and physical–chemical process inducing a tension that favors the release of cytokines, hormones, neurotransmitters and cortisol. The effects of acute stress on the cellular composition and secretion of IgA in large intestine has not yet been described. The secretory IgA plays an important role in host immune response as a first line of defense, including biochemical and cellular defense mechanisms capable of responding rapidly to pathogens. In the present study, acute stress was induced by restriction of movement, and its effect was evaluated in relation to the levels of IgA in intestinal fluid by ELISA and the percentage of T CD4+, T CD8+, B lymphocytes and plasma cells IgA+ in lamina propria by flow cytometry. Serum corticosterone levels were determined to confirm that stress was induced with the model of restraint used and to demonstrate the association of stress with immune system. Corticosterone levels increased in acute stress compared to healthy mice. Significative increase was found in the levels of IgA intestinal fluids. In the large intestine, a increase was observed in CD4+ T cells, CD19+ B cells, and the B220+/CD19+ relation, demonstrating the important role that stress plays in the integrity of the mucosal immune system, as well as its relationship to an increased prevalence of infectious diseases. This work was supported by SIP-COFAA-IPN .

Stress causes an increase in the secretion of glucocorticoid and catecholamine hormones by activation of the hypothalamic-pituitary–adrenal axis. These hormones interact with receptors on immune cells, causing changes in their response. Currently, several illness have been associated with repeated and chronic exposure to stress. Examples are neurodegenerative, cardiovascular, allergic, infectious and inflammatory diseases. However, the mechanisms through which stress can modulate the immune system and cause these pathologies are still completey unknown. The aim of this study was to determine the effect of the acute stress induced by restraint on the immune system associated with the mucosa of the small intestinal of BALB/c mice. Accordingly, a determination was made of the levels of IgA in serum and intestinal fluid of healthy mice and mice subjected to stress by ELISA, the percentage of T helper cells, cytotoxic T and B lymphocytes by flow cytometry, and the concentration of serum corticosterone by the EIA technique. Finally, it was examined whether there is any difference in IgA levels and the percentage of lymphocytes in the small intestine in both study groups. Flow cytometry showed that CD4 + T and B cells increased in the stressed animals in small intestine. Therefore, acute stress induced by restraint increased the secretion of IgA. This work was supported by SIP-COFAA-IPN.

It is known that stress causes significant changes on the immune system through the production of glucocorticoids and catecholamines. The objective of this study was to determined the effect of adrenalectomy on production and secretion of IgA pIgR in the small intestine of BALB/c under acute stress by immobilization 1 h. We considered 5 study groups: (1) control, (2) SHAM (surgery without adrenalectomy) (3) SHAM + E (with stress), (4) Adrenalectomized (ADX), and (5) Stressed Adrenalectomized (ADX + E). In all groups were determined the serum corticosterone levels by EIA, SIgA in intestinal fluid by ELISA and pIgR, IgA and J chain in epithelial cells by Western Blot. The results showed in group SHAM + E an increase in serum corticosterone levels, SIgA in intestinal fluid, IgA, J-chain and pIgR in epithelial cells; The corticosterone ADX levels were near zero; pIgR showed no difference from the control and can be directly related their production to hormonal stimulation. The changes in the morphology and physiology of intestinal epithelium in adrenalectomized mice without stress, favored the increase in the transport of IgA and J chain in epithelial cells, in stress conditions adrenalectomy undergoes further changes in the intestine, explaining why ADX + E group shows no change in the expression of IgA in epithelial cells compared to control groups. This work was supported by SIP-COFAA-IPN.

Stress is considered a disease of our time, affecting a number of people every day, people usually do not understand the stress as something that affects your health. Studies on the effect of stress on the immune system specifically in animal models have shown that the effect varies depending on the type of stress, its duration and if applied acutely or chronically. Changes in cell percentages of different cell populations produced by the application of restraint stress protocol for acute motion has been studied as a reference and in parallel to other parameters such as the effect of hormones, but has not paid sufficient attention to these changes. The aim of this work is to establish changes in the percentages of the populations of LB (B220/CD19), T CD4+ and TCD8+ in Peyer’s patches proximal and distal both during the state of acute stress-induced restriction of movement and during the subsequent recovery status of 2 h. Populations were studied by flow cytometry and corticosterone was measured by enzyme immunoassay (EIA). Flow cytometry showed that CD4+ T, B cells and plasmatic cells IgA+ increased in the stressed animal in Peyer’s patches. Actual changes were observed in lymphocyte populations, but to know the nature of these is necessary for future work studying the degree of apoptosis and the expression of integrins. This work was supported by SIP-COFAA-IPN.

The nose-associated lymphoid tissue (NALT), a compartment located at the base of the nose of some rodents, induces an immune response. Stress causes an increase in the secretion of glucocorticoid and catecholamine hormones by activation of the hypothalamic–pituitary–adrenal axis. The aim of this study was to determine the effects of stress by forced swimming on cell populations of B and T lymphocytes, the secretion of IgA, and the production of corticosterone. We used 10-week-old male BALB/c mice divided into a control group and an experimental group. The secretion of IgA in the nasal wash was determined by ELISA, the cell populations of B and T lymphocytes were quantified by flow cytometry, and the corticosterone levels were measured by an enzyme immunoassay. A significant difference of the secretion of IgA in nasal wash was found in stressed mice. Flow cytometry showed that CD4+ T cells increased in the stressed animals in both the NALT and the spleen, the latter organ representing the control system. We conclude that in response to the acute stressor applied in this study, the NALT showed itself to be sensitive, both in its cellular immune response represented by T lymphocytes as well as its humoral immune response represented by IgA, possibly as a result of the influence of hormones secreted during stress. This work was supported by SIP-COFAA-IPN.

A caloric restriction dietary regimen has been shown to downregulate secretory IgA (SIgA) levels in the proximal and distal segments of the small intestine. Contrarily, both moderate exercise and strenuous exercise upregulate this same parameter, although by distinct mechanisms. The aim of the present study was to assess the effect on SIgA and other mucosal parameters on a mouse model with a protocol of caloric restriction or ad libitum feeding followed by strenuous exercise. After sacrifice an evaluation was made of intestinal SIgA and plasma adrenal hormones (by immunoenzymatic assay), lamina propria IgA plasma-cells (by cytofluorometry), mRNA expression for polymeric immunoglobulin receptor (pIgR), alpha- and J-chains in liver and intestinal mucosa, and pro- and anti-inflammatory cytokines in mucosa samples (by real-time PCR). Caloric restriction showed a net suppressive effect in the proximal small intestine on SIgA production, pIgR transcription and mRNA levels of most IgA producing cytokines, without affecting the mRNA expression of pIgR producing cytokines. Contrarily, caloric restriction had a net stimulatory effect on these same parameters in the distal segment. Compared to the ad libitum group, animals under caloric restriction had lower levels of epinephrine and similar levels of corticosterone. It would thus be interesting to explore the clinical implications of caloric restriction on intestinal homeostasis in a future study, taking into account the distinct response in the proximal and distal segments of the small intestine. This work was supported by SIP and COFAA-IPN.

Diverse studies have shown the effect of acute stress on the immune system. For example, an increase has been observed in IgA levels in the lumen of the small intestine. However, it is not known whether this effect of stress is caused by an increase in the secretion and transport of IgA in the small intestine (SI). The aim of the current study was to determine if stress modifies the secretion and transport of IgA in the duodenum and ileum of the SI in Balb/c mice. Serum samples were obtained for the determination of corticosterone by RIA. Duodenum and ileum were extracted and lymphocytes were obtained from the lamina propia and Peyer’s patches to evaluate the percentage of IgA-producing plasmatic cells by flow cytometry, and epithelial cells were analyzed to measure the expression of pIgR and IgA by Western Blot. The results show that stress increased the levels of serum corticosterone. Additionally an increase in the expression of pIgR was observed in epithelial cells, as well as the percentage of IgA+-producing plasmatic cells in duodenum and ileum. Therefore, acute stress induced by immobilization increased the synthesis, transport and secretion of IgA in both intestinal segments tested, being significantly greater in the ileum. This work was supported by SIP and COFAA-IPN.