Taurine Chloramine Inhibits NO and TNF-α Production in Zymosan Plus Interferon-γ Activated RAW 264.7 Cells
June 2011 | Volume 10 | Issue 6 | Original Article | 659 | Copyright © 2011
Bo Sook Kim,a In Soo Cho,b Seung Yong Park,c Georgia Schuller-Levis,d William Levis,e Eunkyue Parkd
aSeoul Grand Park Zoo, Gwacheon, Gyunggi-do, Korea bNational Veterinary Research and Quarantine Service, Anyang, Gyunggi-do, Korea cCollege of Veterinary Medicine, Konkuk University, Seoul, Korea dDepartment of Developmental Neurobiology, NY State Institute for Basic Research in Developmental Disabilities, Staten Island, NY eDepartment of Dermatology, New York University, New York, NY
Taurine is present abundantly in various tissues, especially in leukocytes embattled to foreign invaders such as microorganisms or oxidants. Taurine-chloramine (Tau-Cl) is produced from taurine at the site of inflammation via the myeoloperoxidase-halide pathway in leukocytes induced by oxidants and/or infectious materials. Previously, our data demonstrated that Tau-Cl inhibited nitric oxide (NO) production and TNF-α secretion induced by lipopolysaccharide (LPS), a Toll-like receptor 4 (TLR-4) ligand or lipoarabinomannan (LAM), a TLR-2 ligand plus interferon-γ (IFN-γ) in peritoneal macrophages or RAW 264.7 cells. Zymosan, a β-glucan of yeast cell wall, is a ligand for TLR-2 and dectin-1 and stimulates macrophages to produce proinflammatory mediators such as NO and TNF-α. Based on our previous data, we examined the effect of zymosan and IFN-γ induced production of NO and TNF-α in the absence or presence of Tau-Cl or taurine using RAW 264.7 cells. Production of NO and secretion of TNF-α is increased when zymosan is combined with IFN-γ. Tau-Cl inhibited production of NO and secretion of TNF-α in zymosan plus IFN-γ activated RAW 264.7 cells in a dose-dependent manner (99% vs. 48% using 0.8mM Tau-Cl). Taurine was without effect. Nitric oxide synthase protein (iNOS), induced by zymosan plus IFN-γ, was inhibited by Tau-Cl (0.8mM) as measured using western blot analysis. NOS mRNA was inhibited by Tau-Cl at four, eight and 16 hours post activation, but not at 24 hours. TNF-α mRNA was inhibited at four hours and eight hours, but not at 16 and 24 hours. These data suggest that expression of both iNOS and TNF-α mRNAs are inhibited by treatment with Tau-Cl within four and eight hours, but not at later time points. Transient suppression of activation of RAW 264.7 cells induced by zymosan may play a critical physiological role for taurine in protecting against tissue injury from initial overt inflammation. This study indicates that tropical treatment of taurine may ameliorate inflammatory dermatoses caused by an environmental yeast or abnormal immune function.
J Drugs Dermatol. 2011;10(6):659-665.
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Higher animals have a limited array of germline encoded pattern recognition receptors (PRRs) that recognize highly conserved microbial structures known as pathogen associated molecular patterns (PAMPs). Engagement of PRRs by microbes or PAMPs directs appropriate innate immune responses and ultimately the development of specific adaptive immunity.1 Toll-like receptors (TLR) are known for the initial recognition of PAMPs and the subsequent signal transduction that determines the ultimate fate of infection. TLR-4 is essential for response to LPS, a major constituent of the outer membrane of Gram-negative bacteria, which is a potent immunostimulatory molecule and cause of septic shock.2 TLR-2 recognizes a wide range of PAMPs derived from various pathogens, ranging from bacteria, fungi, parasites and viruses. Zymosan, a β-glucan of yeast cell wall, is an agonist for TLR-2 and dectin-1 as well as stimulates macrophages to produce NO and TNF-α in various in vivo animal models and/or in vitro cell culture models.3-7 Data show that zymosan directly binds to TLR-2 and produces TNF-α through NF-κ B activation.3 In addition to TLR-2, fungal β-glucans including zymosan, grifolan, curdlan and glucan from baker's yeast also activate NO through a dectin-1 signal pathway.6
Taurine is essential to the development of animals and survival of mammalian cells as well as the most abundant amino acid in leukocytes (20-50 mM) and keratinocytes.8-10 Taurine protects tissues from damage caused from the inflammatory response in a variety of models.11-14 We demonstrated that inflammatory