[13] We have demonstrated

that IL-17A can enhance NO prod

[13] We have demonstrated

that IL-17A can enhance NO production in BCG-infected Silmitasertib price macrophages (Fig. 1). As a result, we are also interested in whether IL-17A can enhance the clearance of intracellular BCG by macrophages. We pre-treated the macrophages with IL-17A for 24 hr, followed by BCG infection. Intracellular BCG was recovered after 2 hr or 48 hr of infection and plated onto 7H10 agar for the determination of phagocytosis or intracellular survival of BCG, respectively. Our data revealed that IL-17A had no effects on phagocytosis of BCG by macrophage (Fig. 5a). On the other hand, the survival of intracellular BCG in macrophages with IL-17A pre-treatment was significantly reduced by 30% after 48 hr of infection (Fig. 5b). The results indicated that IL-17A has anti-mycobacterial effects towards

intracellular BCG. To investigate whether enhanced clearance of intracellular BCG in IL-17A-treated macrophages correlates with NO production, we used AG, a specific iNOS inhibitor, to suppress the enzymatic activity of iNOS.[32] The macrophages were incubated with AG for 1 hr, followed by IL-17A pre-treatment for 24 hr and then BCG infection. The viabilities of macrophages in the presence of AG were analysed by LDH assay. We observed that there was no significant difference in LDH release among the groups, suggesting that the viabilities of macrophages among the groups were similar (Fig. 6a). With the addition of click here AG, we observed that the production of NO in infected macrophages was abolished, regardless of the presence of IL-17A (Fig. 6b). Incubation of macrophages with AG resulted in a 24% increase of intracellular BCG. The same inhibitor also abolished IL-17A-enhanced clearance of intracellular BCG, producing a c.49% increase in intracellular BCG (Fig. 6c). Our Calpain data confirmed that IL-17A-enhanced clearance of intracellular BCG is mediated through an NO-dependent mechanism. In response to microbial infection, macrophages eliminate the phagocytosed pathogens through innate defence mechanisms. The bactericidal effects

of NO on intracellular mycobacteria have long been appreciated in murine models.[12, 33, 34] Unlike murine macrophages, which readily produce NO in response to infections or stimulation, activated human macrophages fail to produce detectable levels of NO in vitro despite iNOS protein expression.[35] Such observations were controversial when regarding the use of NO by human macrophages as an anti-mycobacterial effector. However, several lines of evidence have demonstrated that macrophages isolated from patients with tuberculosis, but not healthy donors, express iNOS and release substantial amounts of NO.[36-38] Further support is provided by studies that use iNOS inhibitors to abolish the killing effects of human macrophages isolated from patients towards intracellular pathogens including BCG and Klebsiella pneumoniae.

Furthermore, even at low doses, remission was durable A total do

Furthermore, even at low doses, remission was durable. A total dose of 8 μg resulted in 53% long-term remission for up to 24 weeks after treatment. This is comparable Ivacaftor purchase to the 56% remission in the 250 μg total dose regimen, despite the difference of > 30-fold in dose. It has been reported that single high doses [one dose of 18–50 μg of anti-CD3 mAb F(ab′)2] produce similarly high remission rates; however, the mice that responded favourably to such treatment were within a very limited glycaemia range (300–349 mg/dl) at the start of treatment, making a direct comparison with our data difficult.24

Various PD parameters were evaluated in mice that received monoclonal anti-CD3 F(ab′)2. Modulation of the CD3–TCR complex on peripheral T cells was dose-dependent. Interestingly, as little as 30% modulation of the CD3–TCR complex, elicited by the 2 μg (4×/72 hr) dose regimen, was sufficient to induce high rates of durable remission in new-onset diabetic NOD mice. The difference in the level of modulation of the CD3–TCR complex between the 2 μg (4×/72 hr) dose regimen and the less effective dose regimen of 1 μg (4×/72 hr) was not large –∼30% versus 20%– but it was statistically significant. We estimate

Tipifarnib order that the 2 μg (4×/72 hr) dose regimen results in having antibody occupy as little as one-fifth of the total number of CD3 molecules in the mouse. Overall, this work demonstrated that in the NOD mouse model: (i) sustained modulation of the CD3–TCR complex during the dosing period was not required for efficacy and remission can occur at lower doses that produce only transient modulation of the CD3–TCR complex, and (ii) partial modulation of the CD3–TCR complex on circulating lymphocytes was sufficient to induce remission. By the end of dosing, there were transient decreases in lymphocyte counts in the peripheral blood, similar to that observed in clinical studies with otelixizumab, but they

were not strictly dose dependent.14 Also, at the end of dosing, there were reductions in the percentages of CD4+ and CD8+ T cells, and a marked increase in the proportion of CD4+ FoxP3+ T cells Parvulin in the peripheral blood. Similar changes have been observed in new-onset type 1 diabetic subjects administered otelixizumab.14 In NOD mice, the altered proportions of T-cell subsets were not strictly dose dependent, although they tended to be more marked at higher doses. Given that similar PD effects occurred in both mice that entered remission and in those that remained diabetic, these PD parameters alone could not be used to predict response to monoclonal anti-CD3 F(ab′)2 treatment in NOD mice.

Negative control sections were stained with isotype immunoglobuli

Negative control sections were stained with isotype immunoglobulin (Ig)G that resulted in no positive staining (data not shown) (samples were observed from all the patients described in the text). Fig. S3. Staphylococcal enterotoxin B (SEB) increases the levels of acid-related orphan receptor (ROR)γt in forkhead box P3 (FoxP3)+

regulatory T cells (Treg). Peripheral blood mononuclear cells Nutlin-3 order (PBMC) were isolated from 10 healthy subjects and cultured in the presence of SEB (10 μg/ml) for 4 days. Cells were collected at the end and analysed by flow cytometry. (a,c) Dot plots indicate CD4+ FoxP3+ Treg before (a) and after (c) culture. (b,d) Histograms indicate RORγt+ Treg (open histograms). The solid histograms MG132 indicate isotype immunoglobulin (Ig)G staining. “
“In a previous study, our group verified that 100% of mice survived to a lethal dose of Candida albicans following pretreatment with concanavalin-A (Con-A) for 3 days. This work proposed

to investigate whether treatment could mediate an adaptative immune response involving TH17 cells. A significant increase in IL-17 levels at 6 h postinfection was observed and was maintained up to 18 h in the Con-A group, whereas in control mice, a reduction in this cytokine was verified. In addition, TH17 cells develop in the presence of TGF-β, IL-1 β, and IL-6 that were increased significantly 2 h postinfection in Con-A-treated mice. Macrophages were involved in the process, engulfing greater numbers of yeast cells, and were activated through TNF-α and interferon-γ produced at significant levels at 2 h postinfection. A significant increase in IL-12 levels was also observed at 2 h postinfection. Thus, activated macrophages were probably more capable of killing and processing Candida antigens, signalizing an adaptative immune response. Macrophages from controls did not prevent yeast-to-hyphae transition and were partially destroyed, as shown

in scanning microscopy. These results suggest that treatment with Con-A many facilitated the triggering of TH17 and TH1 responses via IL-17 and IFN-γ production, leading to the resolution of C. albicans infection. Candida albicans is a commensal organism found in the gastrointestinal and reproductive mucosa; however, in immunocompromised settings, C. albicans leads to oral and oropharyngeal, vulvovaginal, mucocutaneous or disseminated candidiasis (Villar & Dongari-Bagtzoglou, 2008). C. albicans may cause peritonitis when it reaches the peritoneal cavity through iatrogenic inoculation involving contaminated plastic devices and fluids during continuous ambulatory peritoneal dialysis (Michel et al., 1994; Goldie et al., 1996; Fourtounas et al., 2006). The immune responses to these different forms of disease are quite distinct, revealing the complexity of the anatomical basis for host defenses against C. albicans infection.

To lyse contaminating erythrocytes, 1 mL of 0 83% NH4Cl:Tris amin

To lyse contaminating erythrocytes, 1 mL of 0.83% NH4Cl:Tris aminomethane 20.59 g/L, 9:1 (pH 7.2) was mixed with the precipitate and centrifuged at 1500 rpm for 5 mins at 4°C. Finally, the pelleted cells were resuspended in RPMI 1640 medium

with 10% heat inactivated FBS (Biowest, Nuaile, France). Viable cell numbers were counted with a hemocytometer by the trypan blue dye exclusion technique. Splenocytes were seeded in 12-well plates at a concentration of 2 × 107 cells/mL and restimulated with 0.5 mg/mL OVA. The plates were incubated at 37°C in a humidified 5% CO2 environment. The culture supernatants were collected after 24 and 72 hrs for measurement AZD1152HQPA of cytokines. The concentrations of cytokines in the supernatants were assessed by sandwich ELISA according to the manufacturer’s instructions (Duosets; R & D Systems, Minneapolis, MN, USA) and calculated by interpolation of cytokine standard curves. Student’s t-test was used for statistical analysis of the cytokine profiles. click here IL-10, IL-13 and TNF-α were detected in the culture supernatants collected after 24 hrs, whereas IFN-γ and IL-4 were detected in those collected after 72 hrs. As shown in Figure 6, as evidenced by cytokine concentrations in the supernatants of the splenocytes,

there were no significant differences in IL-4, IL-10 or IL-13 production in OVA with pyriproxyfen-immunized mice compared to controls at Weeks 3 or 8. However, mice immunized with OVA with pyriproxyfen showed significantly greater concentrations of TNF-α on both Weeks 3 and 8 (907.9 ± 57.9 and 363.0 ± 72.8 pg/mL, respectively) than did controls (479.6 ± 59.7 and 149.1 ± 34.7 pg/mL; P = 0.04 and P = 0.03, respectively). In addition, as shown in Figure 6, the concentration of TNF-α on Week 3 was significantly higher than that on Week 8 (P = 0.02). The concentrations of IFN-γ were significantly higher at both time points (370.6 ± 45.34 and 273.0 ± 66.2 pg/mL, Temsirolimus datasheet respectively) compared to controls (83.5 ± 29.2 and 68.9 ± 32.9 pg/mL; P = 0.001 and P = 0.01, respectively). In alum containing OVA

immunized mice, the concentrations of IL-4 were significantly higher than those of controls (290.9 ± 22.1 vs. 113.3 ± 5.6 pg/mL; P = 0.001) on Week 8 only. The concentrations of IL-10 were significantly higher (700.2 ± 85.0 and 555.1 ± 32.1 pg/mL, respectively) than those of the controls at both time points (395.1 ± 92.8 and 420.9 ± 20.9 pg/mL, P = 0.04 and P = 0.01, respectively). However, there were no significant differences in production of IL-13 in OVA between alum-immunized mice and controls on Weeks 3 or 8. In the present study, particularly high IgG2a titers and upregulation of TNF-α and IFN-γ were observed in mice immunized with pyriproxyfen along with OVA, but not in those immunized with OVA in alum (Figs. 5 and 6).

The degree of enhancement of sCD93 by PMA in culture supernatants

The degree of enhancement of sCD93 by PMA in culture supernatants from neonatal UCBCs was significantly greater than that of normal adult PBCs and enhancement of sCD93 by PMA in the culture supernatants from neonatal UCBCs www.selleckchem.com/products/Adrucil(Fluorouracil).html and normal adult PBCs was significantly suppressed by PKC inhibitor. Interestingly, the high concentration of serum sCD93 in neonates was significantly decreased in sera from infants at 1 month after birth. Expression of CD93 on the lymphocyte population of PBCs from infants at 1 month after birth was also significantly decreased, compared with that for neonatal UCBCs. These findings

indicate that CD93 in neonatal UCB has unique properties as an immunological biomarker. “
“Implantation is a major landmark in life. It involves the correct apposition of the embryo in the maternal endometrium. The cellular environment influences placenta development, and direct contact of the fetus with maternal tissues is achieved through decidual cells. At the decidua, and at systemic level, the correct balance of cells potentially acting as antigen-presenting cells and histocompatibility products play a pivotal role in achieving feto–maternal tolerance. Here, we review some of the current issues associated with the interplay between Bortezomib cells and molecules needed

for pregnancy development. “
“Paraneoplastic neurologic diseases (PND) involving immune responses directed toward

intracellular antigens are poorly understood. Here, we examine immunity to the PND antigen Nova2, which is expressed exclusively in central nervous system (CNS) neurons. We hypothesized that ectopic expression of neuronal antigen in the heptaminol periphery could incite PND. In our C57BL/6 mouse model, CNS antigen expression limits antigen-specific CD4+ and CD8+ T-cell expansion. Chimera experiments demonstrate that this tolerance is mediated by antigen expression in nonhematopoietic cells. CNS antigen expression does not limit tumor rejection by adoptively transferred transgenic T cells but does limit the generation of a memory population that can be expanded upon secondary challenge in vivo. Despite mediating cancer rejection, adoptively transferred transgenic T cells do not lead to paraneoplastic neuronal targeting. Preliminary experiments suggest an additional requirement for humoral activation to induce CNS autoimmunity. This work provides evidence that the requirements for cancer immunity and neuronal autoimmunity are uncoupled. Since humoral immunity was not required for tumor rejection, B-cell targeting therapy, such as rituximab, may be a rational treatment option for PND that does not hamper tumor immunity.


C12Id-encoded HDAC inhibitors list virus-specific serum Ab, however, were detectable for at least two months after infection, thus appeared relatively long lived (Fig. 1A). Given that serum Ab have a half-life of only a few days in vivo42, 43 and that extrafollicular foci responses are thought to only generate short-lived responses 9, 11, we examined next whether C12Id+ B cells participate also in germinal center reactions, i.e. structures known to provide long-lived immunity. Germinal center development in MedLN was first measurable by day 7 of infection, peaked around day 28, and then remained present for at least 140 days (Fig. 4). C12Id+ B cells with a phenotype consistent

of germinal center B cells (CD45Rhi CD38lo CD24hi Fig. 4) and PNAhi (data not shown) were observed by day 10 of infection. In contrast to the C12Id− responders that showed a time-dependent rise then cessation in the frequencies of germinal center B cells, however, C12Id+ germinal center

B-cell frequencies lacked consistent waxing and waning. Instead they were present only in small frequencies and with irregular kinetics. The relative frequencies of germinal center B cells among the C12Id non-expressers exceeded the frequency of C12Id+ cells at all times after infection (Fig. 4). Given learn more that the virus is cleared from the mice within 7 to 10 days 2, germinal center formation was surprisingly long-lived in the regional LN (still present at low frequencies nearly 5 months after infection). This is consistent with reports on the late induction of influenza-specific memory CD4 T cells from antigen-pools that persist long after influenza virus clearance 44 and suggests that such

antigen-pools must be present in the B-cell follicles of the regional LN. Importantly, the data demonstrate that while C12Id+ B cells participate vigorously in extrafollicular foci responses, they do form germinal centers, albeit at low frequencies and Tangeritin with irregular kinetics. Thus, a population of B cells expressing the same idiotype and recognizing the same epitope on influenza A/PR8 HA is able to initiate both extrafollicular foci and germinal center responses following influenza virus infection. Our studies in T-deficient mice indicated a strong enhancement, but not total dependence of virus-specific C12Id Ab formation on T-cell help (Fig. 1B). Work by others had shown that extrafollicular foci form even in the absence of T cells. In contrast, germinal center formation is dependent entirely on T cells 12, 13. We next aimed to determine whether an increased availability of T-cell help could shift the balance of extrafollicular over germinal center responses toward the latter response. For that we adoptively transferred 2.3×106 TS-1 transgenic CD4 T cells 12 h prior to infection, roughly 40% of which expressed the clonotypic transgenic TCR specific for influenza HA from A/PR8 (45 and data not shown).

(4) “Spontaneous” necrosis and small cell change typically occurr

(4) “Spontaneous” necrosis and small cell change typically occurred away from the Torin 1 purchase intratumoral capillary network embedded within the pattern of GLUT-1 staining. Taken together, GLUT-1 staining cannot be applied as a substitute for histologic grading in order to predict tumor behavior. However, assessment of tumor hypoxia in association with “spontaneous” necrosis and foci of small cell change may substantially contribute to the neuropathologic diagnosis of WHO grades II and III meningioma. “
“We report the clinical and autopsy features of a 65-year-old Japanese man who clinically exhibited overlap of both neuro-Behçet’s disease (NBD) and amyotrophic lateral sclerosis (ALS). The patient had a HLA-B51 serotype,

a recent history of uveitis and had suffered paraparesis, sensory and autonomic disturbance, frontal signs and tremor. A brain and spine MRI study revealed a longitudinally extensive thoracic cord (Th) lesion, but no apparent intracranial abnormalities. The lesion extended ventrally from Th4 to Th9, exhibiting low intensity on T1-weighted images, high intensity on T2-weighted and fluid-attenuated inversion recovery images and gadolinium enhancement.

The patient’s upper and lower motor neuron signs and sensory disturbance worsened and he died 16 months after admission. At autopsy, the spinal cord and brain exhibited characteristic histopathological features of both NBD and ALS, including chronic destruction of the ventral thoracic white and www.selleckchem.com/products/Neratinib(HKI-272).html gray matter, perivascular lymphocytic infiltration, binucleated neurons, lower and upper motor neuron degeneration, Bunina bodies and skein-like inclusions. Although incidental coexistence of these rare disorders could occur in an individual,

this case raises the possibility of a pathomechanistic association between NBD and ALS. “
“R. A. Armstrong, D. Carter and N. J. Cairns (2012) Neuropathology and Applied Neurobiology38, 25–38 A quantitative study of the neuropathology of 32 sporadic and familial cases of frontotemporal lobar degeneration with TDP-43 proteinopathy (FTLD-TDP) Aims: To further characterize the neuropathology of the heterogeneous molecular disorder frontotemporal lobar degeneration (FTLD) with transactive Lumacaftor research buy response (TAR) DNA-binding protein of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). Methods: We quantified the neuronal cytoplasmic inclusions, glial inclusions, neuronal intranuclear inclusions, dystrophic neurites, surviving neurones, abnormally enlarged neurones, and vacuoles in regions of the frontal and temporal lobe using a phosphorylation-independent TDP-43 antibody in 32 cases of FTLD-TDP comprising sporadic and familial cases, with associated pathology such as hippocampal sclerosis (HS) or Alzheimer’s disease (AD), and four neuropathological subtypes using TDP-43 immunohistochemistry. Analysis of variance (anova) was used to compare differences between the various groups of cases.

Significant production of interleukin-12 in the human PBMCs was o

Significant production of interleukin-12 in the human PBMCs was observed after oral administration of Lactobacillus casei spp. casei and L. casei Shirota (Ogawa et al., 2006). The augmentation of phagocytosis activity and the percentage of phagocytotic cells after the probiotic intake compared with the other INCB024360 chemical structure time points demonstrated efficient enhancement of innate immunity in an elderly population after 4 weeks of probiotic cheese consumption. Additionally, the increase in phagocytosis activity related to the consumption of control cheese indicates that the starter strains also have immune stimulation properties at least for the

phagocytosis. The increase in phagocytosis activity might play a role in the observed enhancement of NK cytotoxicity as it has been reported that the phagocytosis of bacteria by monocytes provides an additional signal on accessory cells inducing NK cell activation (Haller et al., 2002). NK cells’ activity is known to be important for immune surveillance against cancer cells and pathogenic infection. The incidence of cancer and the rate of mortality were reported to be higher in populations with a low NK activity compared with those with higher NK activities (Morales & Ottenhof, 1983; Imai et al., 2000; Ogata et al., 2001). Moreover, phagocytosis measurement is a useful tool in the assessment of macrophage function in Selleck Acalabrutinib immunotoxicological and immunopharmacological evaluations (Musclow et al., 1991). However, with the

present findings, further studies are needed to investigate whether there is an association of this size effect of immune modulation with clinical benefits. The general health parameters for the subjects were within

the physiological ranges throughout the course of the study. Although the mean values for erythrocytes, hemoglobin, hematocrit, and % HDL cholesterol were slightly lower after the probiotic intake, they were all within the normal ranges and were not significantly different from the baseline or the wash-out values. The two individuals with high CRP values (43.2 and 50.9 mg L−1) were suffering from urinary tract and respiratory infection, respectively. The values influenced the mean after the consumption of Carnitine palmitoyltransferase II the control cheese so that a significant difference was observed between the baseline and the run-in. A recent study (Hostmark et al., 2009) reported that cheese intake was negatively associated with triacylglycerols and HDL cholesterol. The amount of cheese consumed in this study was constant throughout the study and no correlation could be found between the amount of cheese consumption and the serum lipids. Considering that there were no significant changes in the total cholesterol or the HDL cholesterol level during the study, and the values were in the normal ranges, there seems to be no risk associated with the amount of cheese consumed. However, these values are worthwhile monitoring in future studies when cheese is used as a probiotic carrier.

Visualization of multiple sites around the animals was enhanced w

Visualization of multiple sites around the animals was enhanced with

the use of the Carestream Multimodal Animal Rotation System. “
“The University of Edinburgh, Edinburgh, EH9 3JT, UK Department of Biomedical Sciences and Biotechnology, University of Brescia Medical School, 25123 Brescia, Italy It is well established that tumours hinder both natural and vaccine-induced tumour-specific Dabrafenib CD4+ T-cell responses. Adoptive T-cell therapy has the potential to circumvent functional tolerance and enhance anti-tumour protective responses. While protocols suitable for the expansion of cytotoxic CD8+ T cells are currently available, data on tumour-specific CD4+ T cells remain scarce. We report here that CD4+ T cells sensitized to tumour-associated Ag in vivo, proliferate in vitro in response to IL-7 without the need for exogenous Ag stimulation and accumulate several folds while preserving a memory-like phenotype. Both cell proliferation and survival accounts for the outgrowth of tumour-sensitized T cells among other memory and naive lymphocytes following exposure to IL-7. Also IL-2, previously used to expand anti-tumour CTL, promotes tumour-specific CD4+ T-cell accumulation. However, IL-7 is superior to IL-2 at preserving lymphocyte viability, in vitro and in vivo, maintaining those properties,

that are required by helper CD4+ T cells to confer therapeutic efficacy upon transplantation in tumour-bearing hosts. Together our data support a unique role for IL-7 in retrieving PI3K Inhibitor Library datasheet memory-like CD4+ T cells suitable

for adoptive T-cell therapy. Adoptive cell therapy (ACT) with tumour-specific CD8+ T lymphocytes has become one of the most promising approaches in cancer therapy. Rosenberg et al. first demonstrated the possibility to expand tumour-specific cytotoxic CD8+ lymphocytes (CTL) from tumour lesions in high doses of IL-2 1. These authors later showed that the state of lymphocyte differentiation, induced in the presence of common γ-chain acetylcholine receptor cytokines, is critical for therapeutic efficacy 2, 3. In spite of the recognized importance of Ag-specific CD4+ T cells in both adaptive and innate immune responses, their identification remains elusive, and their in vitro amplification is hindered by the absence of reliable protocols able to support cell proliferation in the absence of terminal differentiation. While, Ag tumours elicit natural tumour-specific CD4+ T-cell responses 4–10, functional tolerance is eventually observed through the induction of T-cell anergy 11, 12, T-cell depletion 13 or the limitation of the memory repertoire 10, 14, 15. This is possibly due to Ag persistence, and continual TCR signaling, as in the case of chronic viral infections 16–18.

This study is a preclinical evaluation of the effect of a combine

This study is a preclinical evaluation of the effect of a combined treatment of α-methyl-prednisolone (PDN) with taurine, a safe aminoacid with positive effects on some pathology-related events. Methods: PDN (1 mg/kg/day i.p.) and taurine (1 g/kg/day orally) were administered either alone or in combination, for 4–8 weeks to male dystrophic mdx mice chronically

exercised on a treadmill. Effects were assessed in vivo and ex vivo with a variety of methodological approaches. Results:In vivo, each treatment significantly CFTR activator increased fore limb strength, a marked synergistic effect being observed with the combination PDN + taurine. Ex vivo, PDN + taurine completely restored the mechanical threshold, an electrophysiological

index of calcium homeostasis, of extensor digitorum longus myofibres and the benefit was greater than for PDN alone. In parallel, the overactivity of voltage-independent cation channels in dystrophic myofibres was reduced. No effects were observed on plasma levels of creatine kinase, while 3-MA mouse lactate dehydrogenase was decreased by taurine and, to a minor extent, by PDN + taurine. A similar histology profile was observed in PDN and PDN + taurine-treated muscles. PDN + taurine significantly increased taurine level in fast-twitch muscle and brain, by high-pressure liquid chromatography analysis. Conclusions: The combination PDN + taurine

has additive actions on in vivo and ex vivo functional end points, with less evident advantages on histopathology and biochemical markers of the disease. X-chromosome gene mutations resulting in the absence of the protein dystrophin cause the severe Duchenne muscular Succinyl-CoA dystrophy (DMD) in humans and dystrophic conditions in animals, such as the mdx mouse [1,2], characterized by progressive muscle weakness and wasting. Dystrophin is a subsarcolemmal component of a multimolecular network (the dystrophin–glycoprotein complex) that ensures a physical linkage between the intracellular cytoskeleton and the extracellular matrix, providing mechanical stability to myofibres during contraction [1]. The absence of dystrophin triggers a complex and still unclear sequence of events that finally lead to progressive myofibre degeneration, failing regeneration and fibrosis. Dystrophin-deficient myofibres show changes in calcium homeostasis, mainly sustained by the increased sarcolemmal influx of calcium ions through voltage-insensitive calcium channels [3–7]. Such changes contribute to modification in excitation-contraction coupling as well as to degeneration through the activation of proteolytic enzymes and/or apoptotic pathways [8–11]. There is also evidence of an early and self-sustained inflammatory response contributing to muscle degeneration and late fibrosis [12–16].