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.

Objectives: To identify relationships between vitamin D serum levels and the presence of autoantibodies directed against vitamin D and levels of interleukin(IL)-17 and IL-23 in patients with systemic lupus erythematosus (SLE). Methods: The study included 49 patients with SLE. Serum concentrations of 25(OH)D 3 were measured with electrochemiluminescence immunoassay (ECLIA). Enzyme-linked immunosorbent assays (ELISA) were used to determine antibodies directed against 1,25(OH) 2 D 3 and levels of IL-17 and IL-23 in serum of SLE patients. In evaluation of vitamin D status, the control group consisted of 49 age and gender matched healthy individuals, whereas in assessment of anti-vitamin D antibodies the control group comprised 30 sera from blood donors. Results: Serum concentration of 25(OH)D 3 in SLE patients during the warm season was 18.47 AE 9.14 ng/ml, which was significantly decreased as compared with that of the control group -31.27 AE 12.65 ng/ml (p ¼ 0.0005). During the cold season a trend toward lower concentration of 25(OH)D 3 in SLE patients was revealed; however, it did not reach statistical significance (11.71 AE 7.21 ng/ml vs. 16.01 AE 8.46 ng/ml; p ¼ 0.054). Results within the recommended range for vitamin D (30-80 ng/ml; 70-200 nmol/l) were observed only in three patients. The 25(OH)D 3 concentration was decreased in SLE patients with renal disease or leucopenia as compared with the levels in patients who did not have either problem (p ¼ 0.006 and p ¼ 0.047, respectively). The cold season was found to be a risk factor for vitamin D deficiency (<20 ng/ml) (odds ratio ¼ 9.25; p ¼ 0.005). Autoantibodies directed against 1,25(OH) 2 D 3 were detected in three SLE patients. No significant difference in 25(OH)D 3 serum concentrations was found between SLE patients with and without these autoantibodies. No link was shown between the existence of autoantibodies against 1,25(OH) 2 D 3 and clinical or laboratory findings, including IL-17 and IL-23 levels. However, serum concentrations of IL-23 were lower in patients with vitamin D deficiency (p ¼ 0.037). Conclusions: SLE patients, especially those with leucopenia or renal involvement, are at high risk of vitamin D deficiency and require vitamin D supplementation. Some SLE patient sera contained 1,25(OH) 2 D 3 antibodies, but these antibodies do not appear to affect vitamin D levels. Lupus (2012) 21, 477-484.

The implication of select protein kinase C (PKC) isoenzymes in cytokine production by human monocytes was investigated using an isozymeselective inhibitor of PKC, rottlerin. We found that lipopolysaccharide (LPS) triggers cytosol-to-membrane translocation of PKC␣ and ␦ isoenzymes, whereas phorbol ester (

The hallmarks of rheumatoid arthritis (RA) are leukocytic infiltration of the synovium and expansiveness of fibroblast-like synoviocytes (FLS). The abnormal proliferation of FLS and their resistance to apoptosis is mediated, at least in part, by present in RA joints proinflammatory cytokines and growth factors. Because IL-15 exerts properties of antiapoptotic and growth factors, and is produced by RA FLS, we hypothesized that IL-15 participates in RA FLS activation. To test this hypothesis, we first examined whether RA FLS express chains required for high affinity functional IL-15R. Indeed, RA FLS express IL-15Rα at mRNA and protein levels. Moreover, we confirmed the presence of IL-2Rβ and common γ-chains. Interestingly, TNF-α or IL-1β triggered significant elevation of IL-15Rα chain at mRNA and protein levels. Next, we investigated the effects of exogenous or endogenous IL-15 on Bcl-2 and Bcl-xL expression, FLS proliferation, and apoptosis. Exogenous IL-15 enhanced RA FLS proliferation and increased the level of mRNA-encoding Bcl-xL. To test the role of endogenous IL-15 in the activation of RA FLS, an IL-15 mutant/Fcγ2a protein exerting properties of specific antagonist to the IL-15Rα chain was used. We found that blocking IL-15 biological activities using this protein substantially reduced endogenous expression of Bcl-2 and Bcl-xL, and RA FLS proliferation that was reflected by increased apoptosis. Thus, we have demonstrated that a distinctive phenotype of RA FLS, i.e., persistent activation, proliferation, and resistance to apoptosis, is related to the autocrine activation of IL-15Rs by FLS-derived IL-15.

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