The suppression of dermatitis by combined therapy was accompanied by a decrease in the plasma level of IgE and in the splenic level of IL-5, IL-13, TARC and eotaxin. Histological finding indicated that the dermal infiltration of inflammatory cells including mast cells and eosinophils was greatly reduced. Particularly, immunohistological evaluation reveals a reduction in CD3+ T cells and CLA+ cells in the combined therapy. Our findings suggest that combination therapy of glucosamine plus FK-506 was more synergistic efficacy than single-modality treatment with either

alone to improve the development of established dermatitis in NC/Nga mice model. This combined immunosuppressive therapy may provide an effective therapeutic strategy for the treatment of AD. Atopic dermatitis GSK2118436 in vivo (AD), or atopic eczema, is a common, chronic, inflammatory skin disease [1, 2]. The worldwide lifetime prevalence of AD in children is 10–20%, and in adults it is 1–3% [3]. Several

lines of evidence suggest the contribution of immunological mechanisms in the pathogenesis of learn more AD. Several immunology reports have suggested T-helper 1 (Th1)/T-helper 2 (Th2) imbalance in AD [4, 5]. This imbalance favours Th2, and high serum immunoglobulin (Ig) E levels as well as infiltration with immune cells such as eosinophils, mast cells and cutaneous lymphocyte antigen (CLA) T cells [6–8], which are all characteristics of AD, are provoked by Th2 cytokines, interleukin-4 (IL-4), IL-5 and IL-13 [9]. Patients with AD show elevated plasma IgE levels in response to many kinds of allergens, while keratinocytes of patients

with AD exhibit the propensity to produce exaggerated amounts of cytokines, a phenomenon that can play a major role in the promotion ADAMTS5 and maintenance of inflammation [10, 11]. Glucosamine is a common constituent of the glycosaminoglycans in the cartilage matrix and synovial fluid. Use of glucosamine is common in patients with osteoarthritis, because of its pharmacological effects on articular cartilage and joint tissue [12, 13]. In fact, its anti-inflammatory activity may allow for reduced doses of non-steroidal anti-inflammatory agents. The suppression of inflammatory activity may result from the potential immunoregulatory capability of glucosamine. It has been reported that glucosamine suppresses proliferation and differentiation of unprimed CD4+ T cells and is more inhibitory towards the development of Th2-mediated immune responses than Th1-mediated immune responses [14]. Thus, glucosamine has immunosuppressive properties also [15]. We recently reported that prophylactic treatment with glucosamine improved clinical symptoms in Dermatophagoides farinae (Df)-induced NC/Nga mice, with reduced infiltration of mast cells and eosinophils into skin, and that it selectively suppressed Th2-mediated immune responses [16].

burgdorferi BBA64 mutant was observed to be severely attenuated in its ability to infect mice when animals were challenged by the natural mode of tick infestation

(Gilmore et al., 2010). The BBA64 mutant was readily acquired by larval ticks and persisted in ticks through molting (Gilmore et al., 2010), suggesting that BBA64 is not necessary for persistence in the tick, but is required for transmission from the tick vector to the mammalian host. Two borrelial proteins, decorin-binding proteins A and B (DbpA and DbpB), have been shown to bind host decorin (Guo et al., 1995). Decorin is a proteoglycan that consists of a protein core substituted with the GAG chains dermatan sulfate or chondroitin sulfate. Decorin interacts with collagen check details fibers and can be found in numerous tissues as a component of the connective tissue. Therefore, by binding decorin, DbpA and DbpB could mediate the interaction between B. burgdorferi and connective tissues. DbpA and DbpB are surface lipoproteins encoded by the dbpB/A operon (BBA24 and BBA25) located on lp54 (Guo et al., 1998; Hagman et al., 1998; Hanson et al., 1998). Both proteins are upregulated on the surface of B. burgdorferi organisms

grown at reduced pH and by a temperature shift from 23 to 37 °C, which suggests an important role for these proteins in the mammalian environment (Carroll et al., 2000; Revel et al., 2002; Ojaimi et al., 2003). The importance of DbpA/B in GAG binding was demonstrated XL765 mouse by expressing DbpA or DbpB in the B. burgdorferi strain B314, an avirulent strain lacking lp54. The B314 strain was able to bind mammalian epithelial 293 cells only when DbpA or DbpB were expressed in this strain (Fischer et al., 2003). Many studies have investigated the role of DbpA/B and decorin binding in the life cycle of B. burgdorferi. Brown and colleagues have demonstrated the importance of B. burgdorferi decorin binding in decorin-deficient mice (Brown Resminostat et al., 2001). Bacterial burden in tissues of decorin-deficient mice were significantly reduced as compared to wild-type mice (Brown et al., 2001; Liang et al., 2004). Needle

inoculation of mice with a DbpA-/DbpB-deficient B. burgdorferi strain demonstrated that DbpA and DbpB are not essential for establishing an infection, but DbpA-/DbpB-mutant strains were attenuated in virulence (Shi et al., 2006, 2008; Weening et al., 2008). Despite the results from needle inoculation experiments, tick infestation studies revealed that DbpA-/DbpB-deficient spirochetes were able to infect mice (Blevins et al., 2008). Collectively, these experiments suggest that DbpA and DbpB play a critical role in later stages of disease, such as during dissemination and establishing a long-term chronic infection in decorin-rich tissues, but that DbpA and DbpB are likely not essential for establishing an infection in mammals.