n-bromotaurine and Inflammation

For one century, taurine is considered as an end product of sulfur metabolism. In this review, we discuss the beneficial effect of taurine, its haloamines and taurine upregulated gene 1 (TUG1) long non‑coding RNA (lncRNA) in both cancer and inflammation. We outline how taurine or its haloamines (N‑Bromotaurine or N‑Chlorotaurine) can induce robust and efficient responses against inflammatory diseases, providing insight into their molecular mechanisms. We also provide information about the use of taurine as a therapeutic approach to cancer. Taurine can be combined with other chemotherapeutic drugs, not only mediating durable responses in various malignancies, but also circumventing the limitations met from chemotherapeutic drugs, thus improving the therapeutic outcome. Interestingly, the lncRNA TUG1 is regarded as a promising therapeutic approach, which can overcome acquired resistance of cancer cells to selected strategies. In this regard, we can translate basic knowledge about taurine and its TUG1 lncRNA into potential therapeutic options directed against specific oncogenic signaling targets, thereby bridging the gap between bench and bedside.

Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Cell Proliferation; Disease Models, Animal; Disease Progression; Drug Resistance, Neoplasm; Gene Expression Regulation, Neoplastic; Humans; Inflammation; Neoplasms; Prognosis; RNA, Long Noncoding; Taurine

This review is an attempt to summarize our knowledge about taurine bromamine (TauBr) properties, its role in innate immunity and its therapeutic potential.TauBr and taurine chloramine (TauCl) are major haloamines generated by eosinophils and neutrophils at a site of inflammation. Both haloamines share anti-inflammatory and anti-oxidant properties. TauBr, similarly to TauCl, decreases the production of proinflammatory mediators. Their anti-inflammatory and anti-oxidant activities are enhanced by their ability to induce the expression of heme oxygenase-1 (HO-1). TauCl is more stable than TauBr. On the other hand, only TauBr was found to be highly membrane-permeable showing stronger microbicidal activity than TauCl.In the light of the anti-inflammatory and antimicrobial properties of TauBr we discuss its therapeutic potential in local treatment of inflammation, especially acne vulgaris, the most common inflammatory skin disorder. TauBr, at non-cytotoxic concentrations, is able to kill Propionibacterium acnes, the skin bacteria involved in pathogenesis of acne vulgaris.As topical antibiotics used in the therapy of acne are associated with the emergence of resistant bacteria, topical TauBr seems to be a good candidate for an alternative therapy.Recently, in a double blind trial, the efficacy of TauBr was compared with the efficacy of clindamycin, one of the most common topical antibiotics used in acne therapy. Comparable reduction of acne lesions was observed in the TauBr and clindamycin groups of patients with mild and moderate inflammatory facial acne vulgaris. We conclude that this pilot study supports our concept that TauBr can be used as a topical agent in the treatment of acne vulgaris, especially in patients who have already developed antibiotic resistance. Further studies are necessary to substantiate the more extended use of TauBr as an anti-inflammatory and anti-oxidant agent in human medicine.

Topics: Acne Vulgaris; Anti-Infective Agents; Anti-Inflammatory Agents; Clinical Trials as Topic; Eosinophils; Humans; Immunity, Innate; Inflammation; Neutrophils; Propionibacterium acnes; Taurine

Taurine chloramine (TauCl) and Taurine bromamine (TauBr), products of the neutrophil myeloperoxidase halide system, exert anti-inflammatory properties. They inhibit the production of a variety of inflammatory mediators, such as prostaglandin E2 (PGE2), nitric oxide (NO) and proinflammatory cytokines. Heme oxygenase-1 (HO-1), a stress inducible enzyme, degrades heme to biliverdin, free iron and carbon monoxide (CO), which are involved in the anti-inflammatory and antioxidant actions of HO-1. Recently we have demonstrated that taurine haloamines induce the expression of HO-1 in inflammatory cells. In this study we examined whether HO-1 participates in taurine haloamines-mediated suppression of proinflammatory cytokine production. We have shown that TauCl/TauBr and CO inhibit the production of TNF-alpha, IL-12 and IL-6, in a similar dose-dependent manner. However, the suppressor activity of TauCl was not altered in HO-1 deficient mice. Therefore, HO-1 and TauCl may independently regulate the production of proinflammatory cytokines. We suggest that TauCl and TauBr provide a link between the two antioxidant systems: the cysteine pathway and the heme oxygenase system.

Topics: Animals; Carbon Monoxide; Cytokines; Enzyme Inhibitors; Heme Oxygenase (Decyclizing); Inflammation; Macrophages; Male; Mice; Mice, Inbred BALB C; Mice, Knockout; Oxidative Stress; Taurine

The myeloperoxidase system of neutrophils generates chlorinating and brominating oxidants in vivo. The major haloamines of the system are taurine chloramine (TauCl) and taurine bromamine (TauBr). It has been demonstrated in vitro that TauCl exerts both antiinflammatory and anti-bacterial properties. Much less is known about TauBr. The present study was conducted to compare bactericidal and immunoregulatory capacity of TauBr with that of the major chlorinating oxidants: HOCl and TauCl. Moreover, the effect of nitrites and H(2)O(2) on TauBr activity was investigated.. TauBr was prepared by reaction of HOBr with taurine. The reaction was monitored by UV absorption spectra.. Bactericidal activity of TauBr, TauCl and HOCl was tested by incubation of E. coli with the compounds and determined by the pour-plate method. To test the anti-inflammatory activity the compounds were incubated with LPS and IFN-gamma stimulated murine peritoneal macrophages. The production of following mediators was measured: nitrites by Griess reaction; TNF-alpha, IL-6, IL-10, IL-12p40 using capture ELISA. In some experiments the compounds were incubated with either nitrites or H(2)O(2).. In our experimental set-up TauBr and HOCl exerted strong bactericidal effects on E. coli (MBC = 110 microM and 8 microM, respectively), while TauCl (< 1000 microM) did not kill test bacteria. However, both, TauBr and TauCl, at noncytotoxic concentrations (< 300 microM) inhibited the cytokine and nitric oxide production by macrophages. H(2)O(2) completely abolished the biological activities of TauBr but not those of TauCl. Nitrites did not affect any activity of TauBr or TauCl while they diminished the HOCl(-) mediated bacterial killing.. TauBr, despite very low concentration of Br(-) in body fluids, may support TauCl and HOCl in the regulation of inflammatory response and in killing of bacteria by neutrophils. However, TauBr activity in vivo will depend on the presence of H(2)O(2) and possible other mediators of inflammation which can compete with target molecules for TauBr.

Topics: Animals; Anti-Bacterial Agents; Cells, Cultured; Cytokines; Drug Interactions; Drug Stability; Hydrogen Peroxide; Inflammation; Macrophages; Male; Mice; Mice, Inbred BALB C; Microbial Sensitivity Tests; Nitrites; Spectrum Analysis; Taurine; Taurocholic Acid

Taurine chloramine (TauCl) and taurine bromamine (TauBr) are products of activated neutrophils and eosinophils, respectively. It has been reported that TauCl, has strong anti-inflammatory properties. In a number of separate studies it has been shown that heme oxygenase-1 (HO-1), a stress inducible protein, exerts similar anti-inflammatory effects. In this study we investigated the influence of HO-1 on TauCl/TauBr mediated suppression of NO generation in J774.2 macrophages. Expression of HO-1 and inducible nitric oxide synthase (NOS-2) in LPS stimulated J774.2 cells provides an opportunity for determining these interactions. TauCl and TauBr, at non-cytotoxic concentrations, in a similar, dose-dependent manner, inhibited the expression of NOS-2, as evidenced by western blotting technique. Surprisingly, TauCl and TauBr induced expression of HO-1 in both non-activated and LPS-activated macrophages. Importantly, the fall in NOS-2 protein level was associated with a concomitant, dose-dependent induction of HO-1. In addition, an inhibitor of HO-1 activity, chromium III mesoporhyrin (CrMP), attenuated the inhibitory activity of TauBr but not that of TauCl, as measured by nitrite accumulation. These results suggest that at a site of inflammation, TauCl and TauBr may provide a link between taurine-dependent and HO-1-dependent cytoprotective mechanisms.

Topics: Animals; Anti-Inflammatory Agents; Blotting, Western; Cell Line; Cell Survival; Dose-Response Relationship, Drug; Enzyme Inhibitors; Gene Expression Regulation, Enzymologic; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Inflammation; Lipopolysaccharides; Macrophages; Membrane Proteins; Mice; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Taurine; Tetrazolium Salts; Thiazoles; Time Factors