Study of Anti-Inflammatory Action of Aurothiomalate,an Inhibitor of NF-κB

We compared the effects of NF-κB inhibitor aurothiomalate and voltaren on NO production by mouse macrophages in vitro, their ability to cause local edema at the site of injection, and their effect on carrageenan-induced inflammation. High concentrations of aurothiomalate reduced NO production, while in low concentrations both aurothiomalate and voltaren stimulated this process. When injected into mouse footpad, aurothiomalate in a dose >1 mM and voltaren in a dose >1.6 μM induce paw edema. Both compounds suppressed carrageenan-induced inflammation, but the efficacy of aurothiomalate 2-fold exceeded that of voltaren.     

Regulation of NF-κB by deubiquitinases

The nuclear factor-κB (NF-κB) pathway is a critical regulator of innate and adaptive immunity. Noncanonical K63-linked polyubiquitination plays a key regulatory role in NF-κB signaling pathways by functioning as a scaffold to recruit kinase complexes containing ubiquitin-binding domains. Ubiquitination is balanced by deubiquitinases that cleave polyubiquitin chains and oppose the function of E3 ubiquitin ligases. Deubiquitinases therefore play an important role in the termination of NF-κB signaling and the resolution of inflammation. In this review, we focus on NF-κB regulation by deubiquitinases with an emphasis on A20 and CYLD. Deubiquitinases and the ubiquitin/proteasome components that regulate NF-κB may serve as novel therapeutic targets for inflammatory diseases and cancer.     

Differentiation of Babesia bigemina, B. bovis, B. divergens and B. major by Western blotting—first report of B. bovis in Austrian cattle

To establish an assay for the serological differentiation of bovine Babesia species (B. bigemina, B. bovis, B. divergens and B. major), antigens from experimentally infected cattle were Western blotted and probed with homologous and heterologous sera. Varying antigen patterns for each species allowed the determination of species-specific diagnostic antigens. Blood samples from 36 naturally infected cattle from the province of Styria were tested by indirect immunofluorescence antibody test (IFAT) against B. divergens, as well as by Western blotting against B. bigemina, B. bovis, B. divergens and B. major, 3 weeks after clinical babesiosis was diagnosed by blood smears. All 36 cattle were B. divergens-positive when tested by IFAT. In four cases (11%), an infection with both B. bovis and B. divergens and in two cases a single infection with B. bovis were diagnosed when tested by Western blot. B. bigemina and B. major infections were not detected. These are the first serologically confirmed cases of B. bovis in Austrian cattle.     

Role of NF-κB in epithelial biology

Since its discovery, nuclear factor-κB (NF-κB) has been recognized as a critical regulator of immune responses. While early studies focused on studying the role of NF-κB in the development and function of immune cells, more recently the function of the inhibitor of NF-κB kinase (IKK)/NF-κB pathway in non-immune cells has gained increased attention. Studies in genetic mouse models were instrumental in dissecting the cell-specific functions of NF-κB and provided experimental evidence that NF-κB signaling in epithelial cells is important for the maintenance of immune homeostasis in barrier tissues such as the skin and the intestine. Increased activation of IKK/NF-κB triggered cytokine expression by the epithelial cells, resulting in exacerbated tissue inflammatory responses. NF-κB inhibition in keratinocytes triggered severe tumor necrosis factor-dependent skin inflammation and epidermal hyperplasia, while inhibition of IKK/NF-κB signaling in intestinal epithelial cells disturbed the intestinal barrier and triggered severe chronic colon inflammation. Therefore, epithelial NF-κB signaling performs critical 'peace keeping' functions in barrier tissues at the interface with the environment by regulating cell survival, barrier integrity, and the immunological and anti-microbial responses of epithelial cells. Improved understanding of epithelial NF-κB functions may hold the key for elucidating the etiology and pathophysiology of chronic inflammatory diseases in epithelial tissues.     

Accumulation of marginal zone B cells and accelerated loss of follicular dendritic cells in NF-κB p50-deficient mice

Background

We previously showed that local use of periodate oxidized ATP (oATP, a selective inhibitor of P2X7 receptors for ATP) in rat paw treated with Freund's adjuvant induced a significant reduction of hyperalgesia Herein we investigate the role of oATP, in the rat paws inflamed by carrageenan, which mimics acute inflammation in humans.

Results

Local, oral or intravenous administration of a single dose of oATP significantly reduced thermal hyperalgesia in hind paws of rats for 24 hours, and such effect was greater than that induced by diclofenac or indomethacin. Following oATP treatment, the expression of the pro-inflammatory chemokines interferon-gamma-inducible protein-10 (IP-10), mon ocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) within the inflamed tissues markedly decreased on vessels and infiltrated cells. In parallel, the immunohistochemical findings showed an impairment, with respect to the untreated rats, in P2X7 expression, mainly on nerves and vessels close to the site of inflammation. Finally, oATP treatment significantly reduced the presence of infiltrating inflammatory macrophages in the paw tissue.

Conclusion

Taken together these results clearly show that oATP reduces carrageenan-induced inflammation in rats.     

Regulation of NF-κB by the CARD proteins

Scaffold proteins play pivotal roles in the regulation of signal transduction pathways by connecting upstream receptors to downstream effector molecules. During the last decade, many scaffold proteins that contain caspase-recruitment domains (CARD) have been identified. Investigating the roles of CARD proteins has revealed that many of them play crucial roles in signaling cascades leading to activation of nuclear factor-κB (NF-κB). In this review, we discuss the contributions of CARD proteins to NF-κB activation in various signaling cascades. In particular, we share some of our personal experiences during the initial investigation of the functions of the CARMA family of CARD proteins and then summarize the roles of these proteins in signaling pathways induced by antigen receptors, G protein-coupled receptors, receptor tyrosine kinase, and C-type lectin receptors in the context of recent progress in these field.     

Effects of the polysaccharides from Spirulina platensis on the activities of hepatitis B virus

It has been well known that hepatitis B virus(HBV) infection can result in acute or chronichepatitis as well as hepatocirrhosis and/or hepato-carcinomainsome cases ,especiallyforthe chron-ic patients [1] . Few drugs can efficiently curechronic hepatitis B (CHB) . Up to now,only in-terferon-αandlamivudine (3TC) were certified byFDAfortreatment CHB.Someinvestigates showedthat the percentage of response to IFN-αwas nomore than 30 %after one year of treatment . Al-though copies of HBV …