Saccharomyces cerevisiae ß-glucan improves the response of trained macrophages to severe P. aeruginosa infections.

OBJECTIVE P. AERUGINOSA: (PA), the major pathogen of lung cystic fibrosis (CF), polarizes macrophages into hyperinflammatory tissue damaging phenotype. The main aim of this study was to verify whether training of macrophages with ß-glucan might improve their response to P. aeruginosa infections. METHODS: To perform this task C57BL/6 mice sensitive to infections with P. aeruginosa were used. Peritoneal macrophages were trained with Saccharomyces cerevisiae ß-glucan and exposed to PA57, the strong biofilm-forming bacterial strain isolated from the patient with severe lung CF. The release of cytokines and the expression of macrophage phenotypic markers were measured. A quantitative proteomic approach was used for the characterization of proteome-wide changes in macrophages. The effect of in vivo ß-glucan-trained macrophages in the air pouch model of PA57 infection was investigated. In all experiments the effect of trained and naïve macrophages was compared. RESULTS: Trained macrophages acquired a specific phenotype with mixed pro-inflammatory and pro-resolution characteristics, however they retained anti-bacterial properties. Most importantly, transfer of trained macrophages into infected air pouches markedly ameliorated the course of infection. PA57 bacterial growth and formation of biofilm were significantly suppressed. The level of serum amyloid A (SAA), a systemic inflammation biomarker, was reduced. CONCLUSIONS: Training of murine macrophages with S. cerevisiae ß-glucan improved macrophage defense properties along with inhibition of secretion of some detrimental inflammatory agents. We suggest that training of macrophages with such ß-glucans might be a new therapeutic strategy in P. aeruginosa biofilm infections, including CF, to promote eradication of pathogens and resolution of inflammation.

Biofilm-forming strains of P. aeruginosa and S. aureus isolated from cystic fibrosis patients differently affect inflammatory phenotype of macrophages.

OBJECTIVE: Lung cystic fibrosis (CF) is characterized by chronic infections and hyperinflammatory response of neutrophils and macrophages. P. aeruginosa (PA) and S. aureus (MSSA, MRSA) are major pathogens of advanced CF. The main goal of this study was to compare the inflammatory phenotype of murine C57BL/6 macrophages exposed to PA57 with that exposed to MSSA60, both strains isolated from the same patient with severe CF. In the present study, we used C57BL/6 mice sensitive to lung infection with P. aeruginosa. METHODS: We measured the release of cytokines and the expression of phenotypic markers of murine neutrophils and macrophages exposed to bacterial cells and biofilm components (i.e., EPS) of the selected bacteria. In addition, a quantitative proteomic approach was used for the characterization of proteome-wide changes in macrophages. RESULTS: Neutrophils stimulated with PA57 and MSSA60 strains produced hyperinflammatory pattern of cytokines. The pro-inflammatory impact of PA57 was significantly higher than that of MSSA60 (IL-6/IL-10 ratio: PA57 = 9.3 vs. MSSA60 = 1.7). Macrophages produced significantly lower amount of cytokines, but showed classical pattern of M1 markers (iNOS-High; arginase-1 and mannose receptor MRC1-Low). Importantly, as evidenced by proteomic analysis, PA57 and PA57-EPS were stronger inducers of M1 macrophage polarization than the MSSA60 counterparts. CONCLUSIONS: Our study demonstrated that strong biofilm P. aeruginosa strains, CF isolates, are dominant inducers of M1 macrophages, termed biofilm-associated macrophages (BAMs). We suggest that repolarization of detrimental BAMs might be a new therapeutic strategy to ameliorate the airway damage in CF.

Current Opinion on the Therapeutic Capacity of Taurine-Containing Halogen Derivatives in Infectious and Inflammatory Diseases.

Taurine haloamines, N-chlorotaurine (NCT, TauCl), and N-bromotaurine (NBT, TauBr) are formed by a reaction between taurine and hypohalous acids, HOCl and HOBr, respectively. The major source of endogenous taurine haloamines is neutrophils. Both NCT and NBT share strong anti-inflammatory and microbicidal activities supported by an absence of microbial resistance. In the light of these properties, a number of clinical studies have been performed to document their effectiveness in treatment of bacterial, fungal, and viral infections. The administration of NCT and NBT has been limited to topical application, as they are decomposed upon systemic delivery. This review summarizes current knowledge concerning the therapeutic use of NCT and NBT mainly in various skin disorders such as non-healing wounds, acne vulgaris, herpes zoster, and psoriasis. Moreover, the beneficial effect of NCT inhalation in early stages of COVID-19 and other viral respiratory infections is discussed. And finally, we would like to suggest that NCT might be used to inhibit the development of the cytokine storm through its capacity to suppress the production of IL-6.

Taurine and N-Bromotaurine in Topical Treatment of Psoriasis.

Psoriasis is a chronic skin auto-inflammatory and systemic disorder. Novel treatments are needed to solve a plethora of cases refractory to current treatment regimens. N-bromotaurine (TauNH-Br), a natural taurine oxidizing derivative produced by inflammatory cells, has anti-inflammatory, antiproliferative, and antimicrobial properties. This evidence prompted us to use TauNH-Br as a local agent for treatment of therapy-refractory psoriasis. Two pustular-plaque psoriasis cases, unresponsive to systemic and local treatments, one with localized lesions and one with generalized lesions, were selected. Both applications primarily indicated a sufficient curative activity of 1% TauNH-Br in psoriasis lesions. Moreover, TauNH-Br co-administration with taurine and a novel olive oil formulation cut in half the time needed for TauNH-Br alone to cause the same regression of equivalent psoriasis plaque lesions in the same patient. Importantly, all adverse effects of TauNH-Br (erythema, itching, bleeding) could be minimized by the combination therapy. Periods of 2-7 weeks to achieve almost complete regression with this formulation were remarkably short as compared to conventional treatment regimens that both patients had followed previously. Of note, there was no relapse within 3 months of monitoring. Combination formulations containing TauNH-Br and olive oil could become an advantageous topical medication for treatment of psoriasis.

Immunomodulatory Activity of the Most Commonly Used Antihypertensive Drugs-Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers.

This review article is focused on antihypertensive drugs, namely angiotensin converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARB), and their immunomodulatory properties reported in hypertensive patients as well as in experimental settings involving studies on animal models and cell lines. The immune regulatory action of ACEI and ARB is mainly connected with the inhibition of proinflammatory cytokine secretion, diminished expression of adhesion molecules, and normalization of CRP concentration in the blood plasma. The topic has significant importance in future medical practice in the therapy of patients with comorbidities with underlying chronic inflammatory responses. Thus, this additional effect of immune regulatory action of ACEI and ARB may also benefit the treatment of patients with metabolic syndrome, allergies, or autoimmune disorders.

Chronic bacterial pulmonary infections in advanced cystic fibrosis differently affect the level of sputum neutrophil elastase, IL-8 and IL-6.

Advanced cystic fibrosis (CF) lung disease is commonly characterized by a chronic Pseudomonas aeruginosa infection and destructive inflammation caused by neutrophils. However, the lack of convincing evidence from most informative biomarkers of severe lung dysfunction (SLD-CF) has hampered the formulation of a conclusive, targeted diagnosis of CF. The aim of this study was to determine whether SLD-CF is related to the high concentration of sputum inflammatory mediators and the presence of biofilm-forming bacterial strains. Forty-one patients with advanced CF lung disease were studied. The severity of pulmonary dysfunction was defined by forced expiratory volume in 1 second (FEV1) < 40%. C-reactive protein (CRP) and NLR (neutrophil-lymphocyte ratio) were examined as representative blood-based markers of inflammation. Expectorated sputum was collected and analysed for cytokines and neutrophil-derived defence proteins. Isolated sputum bacteria were identified and their biofilm-forming capacity was determined. There was no association between FEV1% and total number of sputum bacteria. However, in the high biofilm-forming group the median FEV1 was < 40%. Importantly, high density of sputum bacteria was associated with increased concentrations of neutrophil elastase and interleukin (IL)-8 and low concentrations of IL-6 and IL-10. The low concentration of sputum IL-6 is unique for CF and distinct from that observed in other chronic pulmonary inflammatory diseases. These findings strongly suggest that expectorated sputum is an informative source of pulmonary biomarkers representative for advanced CF and may replace more invasive bronchoalveolar lavage analysis to monitor the disease. We recommend to use of the following inflammatory biomarkers: blood CRP, NLR and sputum elastase, IL-6, IL-8 and IL-10.

Anti-Inflammatory Activities of Captopril and Diuretics on Macrophage Activity in Mouse Humoral Immune Response.

Hypertension is accompanied by the over-activation of macrophages. Diuretics administered alone or in combination with hypotensive drugs may have immunomodulatory effects. Thus, the influence of tested drugs on mouse macrophage-mediated humoral immunity was investigated. Mice were treated intraperitoneally with captopril (5 mg/kg) with or without hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) by 8 days. Mineral oil-induced peritoneal macrophages were harvested to assess the generation of cytokines in ELISA, and the expression of surface markers was analyzed cytometrically. Macrophages were also pulsed with sheep red blood cells (SRBC) and transferred to naive mice for evaluation of their ability to induce a humoral immune response. Tested drugs increase the expression of surface markers important for the antigen phagocytosis and presentation. SRBC-pulsed macrophages from mice treated with captopril combined with diuretics increased the secretion of antigen-specific antibodies by recipient B cells, while macrophages of mice treated with hydrochlorothiazide or furosemide with captopril increased the number of antigen-specific B cells. Tested drugs alter the macrophage secretory profile in favor of anti-inflammatory cytokines. Our results showed that diuretics with or without captopril modulate the humoral response by affecting the function of macrophages, which has significant translational potential in assessing the safety of antihypertensive therapy.

Captopril Combined with Furosemide or Hydrochlorothiazide Affects Macrophage Functions in Mouse Contact Hypersensitivity Response.

Hypertension is a chronic disease associated with chronic inflammation involving activated macrophages. Antihypertensive drugs (for example, angiotensin-converting enzyme inhibitors-ACEIs) used in the treatment of hypertension have immunomodulatory properties. On the other hand, the immunological effect of diuretics and combined drugs (diuretics + ACEI) is unclear. Therefore, we examined the influence of diuretics and combination drugs (ACEI + diuretic) on cellular response (contact hypersensitivity), production of reactive oxygen intermediates (ROIs), and nitric oxide (NO), and the secretion of interleukin-12 (IL-12). CBA mice were administered i.p. captopril (5 mg/kg) with or without hydrochlorothiazide (10 mg/kg) or furosemide (5 mg/kg) for 8 days. On the third day, the mice were administered i.p. mineral oil, and macrophages were collected 5 days later. In the presented results, we show that diuretics administered alone or with captopril increase the generation of ROIs and reduce the formation of NO by macrophages. Moreover, tested drugs inhibit the secretion of IL-12. Diuretics and combined drugs reduce the activity of contact hypersensitivity (both activation and induction phases). Our research shows that the tested drugs modulate the cellular response by influencing the function of macrophages, which is important in assessing the safety of antihypertensive therapy.

The dual role of the immune system in the course of COVID-19. The fatal impact of the aging immune system.

COVID-19 is a highly contagious respiratory disease caused by the novel coronavirus SARS-CoV-2. Since October 2020 the second wave of the pandemic has been observed around the world, as pathogen specific herd immunity has not been built yet. Moreover, the current, more contagious pathogen carrying the D614G mutation has become the globally dominant form of SARS-CoV-2. In this article we present the current state of knowledge on the impact of ACE2 and the reninangiotensin system (RAS) and the innate immune system on different outcomes of COVID-19. Especially, we point out the dual role of the immune system and ACE2 in pathogenesis of the disease. Namely, at the initial stage of the infection anti-viral activity of innate immunity is responsible for inhibition of SARS-CoV-2 replication. On the other hand, a dysregulated immune response may cause the detrimental hyperinflammation ("cytokine storm") responsible for the severe course of the disease. Concomitantly, we analyse the roles of ACE2 in both facilitation of infection and abrogation of its effects, as the major cellular entry receptor for SARS-CoV-2 and an important enzyme responsible for tissue protection, respectively. Finally, we discuss the dominant impact of aging on the fatal outcome of COVID-19.

Pseudomonas aeruginosa biofilm is a potent inducer of phagocyte hyperinflammation.

OBJECTIVE: Pseudomonas aeruginosa effectively facilitate resistance to phagocyte killing by biofilm formation. However, the cross talk between biofilm components and phagocytes is still unclear. We hypothesize that a biofilm provides a concentrated extracellular source of LPS, DNA and exopolysaccharides (EPS), which polarize neighbouring phagocytes into an adverse hyperinflammatory state of activation. METHODS: We measured the release of a panel of mediators produced in vitro by murine neutrophils and macrophages exposed to various biofilm components of P. aeruginosa cultures. RESULTS: We found that conditioned media from a high biofilm-producing strain of P. aeruginosa, PAR5, accumulated high concentrations of extracellular bacterial LPS, DNA and EPS by 72 h. These conditioned media induced phagocytes to release a hyperinflammatory pattern of mediators, with enhanced levels of TNF-α, IL-6, IL12p40, PGE2 and NO. Moreover, the phagocytes also upregulated COX-2 and iNOS with no influence on the expression of arginase-1. CONCLUSIONS: Phagocytes exposed to biofilm microenvironment, called by us biofilm-associated neutrophils/macrophages (BANs/BAMs), display secretory properties similar to that of N1/M1-type phagocytes. These results suggest that in vivo high concentrations of LPS and DNA, trapped in biofilm by EPS, might convert infiltrating phagocytes into cells responsible for tissue injury without direct contact with bacteria and phagocytosis.

Combined Biological Effects of N-Bromotaurine Analogs and Ibuprofen. Part I: Influence on Inflammatory Properties of Macrophages.

Taurine haloamines (N-chlorotaurine, N-bromotaurine) due to their strong antiseptic and anti-inflammatory properties are good candidates for topical application in treatment of skin inflammatory/infectious disorders. Recently, we have demonstrated that more stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine) and bromamine T show strong microbicidal and anti-inflammatory properties at concentrations well tolerated by human cells and tissue. Non-steroidal anti-inflammatory drugs (NSAIDs) with cyclooxygenase (COX) inhibitory activity are commonly used in various inflammatory diseases. However, systemic administration of NSAIDs may result in adverse side effects. For example, the use of ibuprofen in children with varicella is associated with enhanced serum levels of TNF-α and with increased risk of necrotizing soft tissue infections and secondary skin infections caused by invasive streptococci. The aim of this study was to examine combined immunomodulatory effects of bromamines and ibuprofen on J774.A1 macrophages. We have shown that the primary activity of ibuprofen, the inhibition of PGE2 production by activated macrophages was intensified in the presence of bromamines. Most importantly, the stimulatory effect of ibuprofen on production of inflammatory cytokines (TNF-α, IL-6) was inhibited by all tested bromamines. These observations indicate that bromamines may neutralize massive production of TNF-α at sites of inflammation, a side effect of ibuprofen. Therefore, we suggest that systemic administration of ibuprofen (NSAIDs) in treatment of inflammatory/infectious skin diseases should be supported by topical application of bromamines as an adjunctive therapy.

Combined Biological Effects of N-Bromotaurine Analogs and Ibuprofen. Part II: Influence on a Local Defense System.

The stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine), and bromamine T (BAT) show anti-inflammatory and microbicidal properties. These bromamines are good candidates for a treatment of skin infectious/inflammatory diseases as local antiseptics. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is commonly used in various infectious/inflammatory diseases due to its analgesic and antipyretic therapeutic effects. However, systemic administration of ibuprofen may also result in adverse side effects. It has been reported that ibuprofen enhances serum levels of TNF-α and worsens secondary skin infections caused by invasive streptococci (S. pyogenes). Recently we have demonstrated that bromamines inhibit the stimulatory effect of ibuprofen on the production of inflammatory cytokines (TNF-α, IL-6). The aim of this study was to examine the combined antibacterial actions of ibuprofen and bromamines against S. pyogenes and their joint effect on the generation of reactive oxygen species (ROS) by activated neutrophils and macrophages. We have shown that the microbicidal activity of bromamines against S. pyogenes was not altered by ibuprofen. On the other hand, co-administration of ibuprofen and bromamines markedly decreased the generation of ROS by activated neutrophils and macrophages. Finally, we discuss how the antioxidant combined effect of bromamines and ibuprofen may affect a local defense system.

Air particulate matter SRM 1648a primes macrophages to hyperinflammatory response after LPS stimulation.

OBJECTIVE: Exposure to air particulate matter (PM) is associated with chronic inflammatory and autoimmune diseases. Macrophages are responsible for the regulation of chronic inflammation. However, whether PM affects macrophage polarization remains unclear. The aim of this study was to evaluate whether nontoxic concentrations of urban PM are able to prime macrophages to altered inflammatory response upon LPS challenge. METHODS: We used two forms of the urban particulate matter SRM 1648a, intact PM and PM deprived of organic compounds (PM∆C). Peritoneal murine macrophages were exposed to different concentrations of PM for 24 h and then challenged with LPS. Production of inflammatory mediators by macrophages was measured to test immunostimulatory/priming capacity of PM. RESULTS: Particulate matter used at non-cytotoxic concentrations induced a dose-dependent production of proinflammatory cytokines (TNF-α, IL-6, IL-12p40). By contrast, PM∆C were not able to stimulate macrophages. However, macrophages primed with both forms of PM show proinflammatory response upon LPS challenge. CONCLUSIONS: Our data indicate that exposure of macrophages to low concentrations of PM may prime the cells to hyperinflammatory response upon contact with LPS. Further studies are necessary to explain whether the exposure of patients suffering from chronic inflammatory diseases to particulate matter is responsible for the exacerbation of clinical symptoms during bacterial infections.

Phagocytosis of live versus killed or fluorescently labeled bacteria by macrophages differ in both magnitude and receptor specificity.

Scavenger receptor (SR)-mediated opsonin-independent phagocytosis of bacteria by macrophages has been suggested to represent an important, early mechanism of anti-bacterial host defense. However, although the ability to bind bacteria has been demonstrated to be a shared feature of all types of SRs, in many cases the evidence is limited to the demonstration of increased binding of killed, fluorescently labeled bacteria to non-phagocytic cells transfected with these receptors. We sought to verify the ability of SRs to mediate non-opsonic phagocytosis of live Escherichia coli (Ec) and Staphylococcus aureus (Sa), model species of Gram-negative and -positive bacteria, respectively, and to assess the relative contributions of different SRs expressed on murine macrophages in this process. We found that the class A SR SR-A/CD204 was the major receptor mediating phagocytosis of fluorescently labeled Sa, whereas different SRs had highly redundant roles in the phagocytosis of live Sa. Conversely, different SRs contributed to the phagocytosis of fluorescently labeled Ec. In comparison, phagocytosis of live Ec was of much lower magnitude and was selectively mediated by SR-A. These results question the use of fluorescently labeled bacteria as valid replacements for live bacteria. The low magnitude of opsonin-independent phagocytosis of Ec and unimpaired phagocytosis of Sa in SR-A- or CD36-deficient macrophages indicate that the defect in this process might not be responsible for the reported impaired bacteria clearance in mice deficient in these receptors. We postulate that this impairment might result to a larger extent from inhibition of intracellular bacteria killing caused by pro-inflammatory cytokines, produced in excessive amounts by SR-deficient cells in response to bacterial products.

Air pollution, oxidative stress, and exacerbation of autoimmune diseases.

A number of epidemiological studies have shown a strong association between exposure to ambient airborne particulate matter (PM 2.5, PM < 1.0) and lung or cardiovascular diseases characterised by high mortality and morbidity. However, much less is known about the role of air pollution in the pathogenesis of autoimmune diseases, which constitutes a significant problem in modern society. This paper summarises the state of current research regarding the influence of PM on the development and/or progression of autoimmune diseases. A brief review of the great body of research concerning pathogenesis of autoimmune disorders is presented. Then, the scope of our review is narrowed to the research related to the impact of particulate matter on oxidative and nitrosative stress, as well as exacerbation of chronic inflammation, because they can contribute to the development of autoimmune diseases. Moreover, we discuss the impact of various components of PM (metal, organic compounds) on PM toxicity and the ability to generate oxidants.

The impact of lactoferrin with different levels of metal saturation on the intestinal epithelial barrier function and mucosal inflammation.

Translocation of bacteria, primarily Gram-negative pathogenic flora, from the intestinal lumen into the circulatory system leads to sepsis. In newborns, and especially very low birth weight infants, sepsis is a major cause of morbidity and mortality. The results of recently conducted clinical trials suggest that lactoferrin, an iron-binding protein that is abundant in mammalian colostrum and milk, may be an effective agent in preventing sepsis in newborns. However, despite numerous basic studies on lactoferrin, very little is known about how metal saturation of this protein affects a host's health. Therefore, the main objective of this study was to elucidate how iron-depleted, iron-saturated, and manganese-saturated forms of lactoferrin regulate intestinal barrier function via interactions with epithelial cells and macrophages. For these studies, a human intestinal epithelial cell line, Caco-2, was used. In this model, none of the tested lactoferrin forms induced higher levels of apoptosis or necrosis. There was also no change in the production of tight junction proteins regardless of lactoferrin metal saturation status. None of the tested forms induced a pro-inflammatory response in Caco-2 cells or in macrophages either. However, the various lactoferrin forms did effectively inhibit the pro-inflammatory response in macrophages that were activated with lipopolysaccharide with the most potent effect observed for apolactoferrin. Lactoferrin that was not bound to its cognate receptor was able to bind and neutralize lipopolysaccharide. Lactoferrin was also able to neutralize microbial-derived antigens, thereby potentially reducing their pro-inflammatory effect. Therefore, we hypothesize that lactoferrin supplementation is a relevant strategy for preventing sepsis.

Staphylococcus epidermidis and biofilm-associated neutrophils in chronic rhinosinusitis. A pilot study.

A key role of bacterial biofilm in the pathogenesis of chronic rhinosinusitis (CRS) with (CRSwNP) and without nasal polyps (CRSsNP) is commonly accepted. However, the impact of some bacterial species isolated from inflamed sinus mucosa on biofilm formation is unclear. In particular, the role of Staphylococcus epidermidis as aetiological agents of CRS is controversial. Moreover, the effect of biofilm formation on neutrophil infiltration and activity in CRSwNP calls for explanation. In this study, biofilms were found in three of 10 patients (mean age = 46 ± 14) with CRS undergoing endoscopic sinus surgery by means of scanning electron microscopy. Unexpectedly, S. epidermidis was the primary isolated bacteria and was also found to be present in all biofilm-positive mucosa specimens, indicating its pivotal role in the pathogenesis of severe chronic infections associated with biofilm formation. We have also measured the activity of myeloperoxidase (MPO), the most abundant neutrophil enzyme, to demonstrate the presence of neutrophils in the samples tested. Our present results show that the level of MPO in CRS associated with biofilm is lower than that without biofilm. It may suggest either a low number of neutrophils or the presence of a type of neutrophils with compromised antimicrobial activity, described as biofilm-associated neutrophils (BAN). Finally, we conclude that further studies with a large number of CRS cases should be performed to establish the association between S. epidermidis and other frequently isolated bacterial species from paranasal sinuses, with the severity of CRS, biofilm formation and the infiltration of BAN.

Pan_02 murine pancreatic cancer model.

AIM: The aim of this study was to investigate and describe basic features of Pan_02 murine pancreatic ade- nocarcinoma tumor model. Pan_02 has very low sensitivity to chemotherapeutics therefore it is very similar to human pancreatic cancers. MATERIALS AND METHODS: Mice were subcutaneously injected with different number of cells and tumor growth was measured. Tumors were also investigated with ultrasonograph VEVO2100 in doppler mode to detect viable and function- al blood vessels. Collected tumor samples were investigated to asses necrosis and blood vessel permeability. RESULTS: We found substantial differences in tumor growth depending on a number of inoculated tumor cells. Mice injected with 0.5 × 106 cells gave the most consistent pattern of growth. All tumors showed substantial vascularisation but bigger tumors were more likely to develop larger blood vessels instead of a more dense network. CONCLUSIONS: Murine Pan_02 cancer model shares many features with human PDAC cancers and therefore it is a good model to study new drugs. Injection of 0.5 × 106 cells gives consistent results although it requires more time for the tumor to grow. It also allows the immune system to adapt. Owing ta good vascularisation, Pan_02 is a good model to study chemotherapy against pancreatic adenocarcinoma but it may not be the best model for immunotherapy since it does not respond to the immune stimulation (unpublished data).

Distinct effects of Lactobacillus plantarum KL30B and Escherichia coli 3A1 on the induction and development of acute and chronic inflammation.

OBJECTIVE: Enteric bacteria are involved in the pathogenesis of ulcerative colitis. In experimental colitis, a breakdown of the intestinal epithelial barrier results in inflow of various gut bacteria, induction of acute inflammation and finally, progression to chronic colitis. MATERIAL AND METHODS: In the present study we compared pro-inflammatory properties of two bacterial strains isolated from human microbiome, Escherichia coli 3A1 and Lactobacillus plantarum KL30B. The study was performed using two experimental models of acute inflammation: peritonitis in mice and trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats. RESULTS: Both bacterial strains induced massive neutrophil infiltration upon injection into sterile peritoneal cavity. However, peritoneal exudate cells stimulated in vitro with E. coli 3A1, produced far more nitric oxide, than those stimulated with L. plantarum KL30B. Interestingly, distinct effect on the development of TNBS-induced colitis was observed after oral administration of the tested bacteria. Lactobacillus plantarum KL30B evoked strong acute colitis. On the contrary, the administration of E. coli 3A1 resulted in a progression of colitis to chronicity. CONCLUSIONS: Our results show that distinct effects of bacterial administration on the development of ongoing inflammation is strain specific and depends on the final effect of cross-talk between bacteria and cells of the innate immune system.

Taurine and inflammatory diseases.

Taurine (2-aminoethanesulfonic acid) is the most abundant free amino acid in humans and plays an important role in several essential biological processes such as bile acid conjugation, maintenance of calcium homeostasis, osmoregulation and membrane stabilization. Moreover, attenuation of apoptosis and its antioxidant activity seem to be crucial for the cytoprotective effects of taurine. Although these properties are not tissue specific, taurine reaches particularly high concentrations in tissues exposed to elevated levels of oxidants (e.g., inflammatory cells). It suggests that taurine may play an important role in inflammation associated with oxidative stress. Indeed, at the site of inflammation, taurine is known to react with and detoxify hypochlorous acid generated by the neutrophil myeloperoxidase (MPO)-halide system. This reaction results in the formation of less toxic taurine chloramine (TauCl). Both haloamines, TauCl and taurine bromamine (TauBr), the product of taurine reaction with hypobromous acid (HOBr), exert antimicrobial and anti-inflammatory properties. In contrast to a well-documented regulatory role of taurine and taurine haloamines (TauCl, TauBr) in acute inflammation, their role in the pathogenesis of inflammatory diseases is not clear. This review summarizes our current knowledge concerning the role of taurine, TauCl and TauBr in the pathogenesis of inflammatory diseases initiated or propagated by MPO-derived oxidants. The aim of this paper is to show links between inflammation, neutrophils, MPO, oxidative stress and taurine. We will discuss the possible contribution of taurine and taurine haloamines to the pathogenesis of inflammatory diseases, especially in the best studied example of rheumatoid arthritis.