Postoperatively 400 mg day−1 of VORI was continued for 4 months. Three months after cessation of VORI treatment (October 2003), ulcerous, inflamed skin lesion appeared on patient’s

upper leg. Again microbiological culture proved P. apiosperma as cause of infection. The isolate was again tested in vitro and had a Trichostatin A nmr MIC for VORI of 1 mg l−1. Extensive debridement was performed, since other case studies report only a successful cure when surgical excision of all infected tissues and antifungal therapy is combined.23,24 The debrided tissue was found by histological examination to contain fungal elements including conidia (Fig. 5). Therefore, antifungal therapy was restarted as combination of VORI (2 dd of 200 mg) and terbinafine (2 dd of 250 mg), as in vitro studies25 and previous cases reported favourable outcomes of Scedosporium infections with azole–terbinafine drug combinations.26–28 He was treated for 6 months after which he remained symptom free for a year until 2005 when he experienced a renewed infection (beside

bacteria no fungi were cultured) for which a re-amputation was necessary. The same surgical procedure was necessary twice in 2007, both times with negative fungal cultures. In 2008, the amputation wound was finally dry and closed. At follow-up in January 2011 the patient is asymptomatic and had experienced no recurrence since two years, but he is confined to a wheelchair because a prosthesis is technically not feasible due to the short stump and the poor condition of the soft tissues. To selleck compound the best of our knowledge this case represents the first report of a PJI in an immunocompetent patient involving a Pseudallescheria/Scedosporium species. The source of infection was not identified. The patient had no conspicuous clinical history, beside a car accident one month before surgery. He neither aspirated water during the car accident, nor Apoptosis inhibitor suffered from deep wounds or other injuries, beside a whiplash. Therefore, injuries resulting from the car accident can be excluded as source of infection. More likely the patient was infected during the surgical procedure or he contaminated the

postoperative wound during his daily work as a cattle farmer. Wound contamination with animal dung might represent the most likely source of infection in this case. Up to now, Scedosporium-arthritis was always reported following a traumatic inoculation of Scedosporium-contaminated materials,13,18,29 but was never reported associated with a joint prosthesis. Scedosporium was four times earlier described as agent of postoperative infections around prostheses in immunocompromised patients. A double endobronchial prosthesis in a bilateral lung transplant recipient,6 an implantable cardioverter-defibrillator,7 and two cases of prosthetic valve endocarditis due to Scedosporium were reported.8,9 The immunocompetent patient in this case repetitively developed ulcerous skin lesions, fistula and pus-filled tissue pockets.

The first is clonal deletion. Although it can be very effective, when actually studied in the periphery it seems to take a very long time to eliminate the autoreactive population [5]. In cases where

the antigen is chronic, this presents a problem since the animal continues to suffer a risk of autoimmunity while the cells are being “slowly deleted.” Therefore, two other processes are thought to operate to keep the cells in check — a functional inactivation, originally termed anergy and the action of Treg cells [6, 7]. However, a clear separation between the three processes in vivo and an understanding of the principles that Akt inhibitor lead to the choice of any one or a combination of them is still lacking. We have previously reported that adoptively transferring antigen specific T cells to mice expressing their target antigen resulted in the induction of anergy and “slow deletion”, but not of Treg cells [5]. Typically, these studies involved the infusion of 1–3 million TCR transgenic T cells to GW-572016 nmr congenic hosts. About 10% of the injected cells effectively incorporate into the secondary lymphoid organs. Nevertheless, work from several labs (using acute immunization, not chronic or self-antigens)

subsequently suggested that at such high frequencies, the T-cell responses were severely constrained by interference between the transferred T cells themselves [8-14]. This phenomenon, termed clonal competition, affects the robustness of the initial T-cell response, the subsequent survival of the activated T cells (memory) and even the extent of differentiation into different subsets [13, 15]. We therefore wondered if such a “precursor frequency effect” could also influence the behavior of self-reactive T cells. Interestingly, we find that chronic antigen stimulation elicits a precursor frequency independent response pattern, compared to an acute challenge. In the latter case the expansion phase and to a much lesser extent, the

onset of contraction was influenced by how many T cells participated in the original response. However, the self-reactive T cells were only minimally affected by precursor frequency during the initial expansion phase. Buspirone HCl Furthermore, in the later phase, recipients seeded with about a 100 self-reactive T cells showed no evidence of clonal deletion for over 4 months. But, even at lower frequency, the self-reactive T cells entered an anergic state marked by reduced recall cytokine production and no conversion to Foxp3 positivity. These data suggest that in the normal repertoire, T cells reactive to chronic self-antigens that escape thymic deletion can respond and persist in the periphery, albeit in an anergic state. The impact of initial precursor frequency on the magnitude of the subsequent T-cell response was modeled using an adoptive transfer strategy wherein log dilutions of congenically marked naïve T cells were injected intravenously into recipient mice and challenged in vivo.

NCGN occurred in mice that had received BM from wild-type, but not from PI3Kγ gene-deleted mice. Moreover, a γ isoform-specific inhibitor abrogated ANCA-induced superoxide generation, degranulation and neutrophil migration in vitro and oral treatment with this compound prevented NCGN in mice, suggesting that specific PI3Kγ inhibition could be

used therapeutically (Fig. 3). Several investigators have now implicated the participation of complement activation in ANCA-induced inflammation. In fact, animal studies narrowed the alternative pathway and particularly C5 as an important component in ANCA-induced NCGN [69,70]. In-vitro experiments elucidated that C5a is generated by ANCA-activated neutrophils and that this component further MG-132 datasheet provides additional neutrophil priming for ANCA activation. Thus, ANCA-induced C5a would then act as an acceleration loop, further enhancing inflammation. C5a is connected to the important PI3K pathway in that the C5a receptor belongs to the G protein-coupled receptors that signal via PI3Kγ[71]. www.selleckchem.com/products/Everolimus(RAD001).html Importantly, mice lacking the C5a receptor in myeloid cells only were protected from anti-MPO antibody-induced NCGN [6]. These data imply that the C5a receptor may provide an additional treatment target in patients with ANCA vasculitis. ANCA stimulation induces neutrophils and monocytes to produce and release cytokines

[44,72–74]. Proinflammatory IL-1β may be of particular clinical interest because it is increased by ANCA, the lack of IL-1βR in renal cells protected from glomerular injury in murine anti-GBM model and an IL-1R blocker is available in the clinic [72,75,76]. Active IL-1β is generated from inactive precursor pro-IL-1β. The classical enzyme that mediates this process is caspase-1. Alternative IL-1β converting enzymes were suggested. We showed Sunitinib recently that active neutrophil serine proteases (NSPs) are critical for IL-1β generation in ANCA-stimulated monocytes and neutrophils. The IL-1β amount produced by monocytes was clearly higher compared to neutrophils, but neutrophils outnumber monocytes in vivo, suggesting that both cell types are possibly important.

Murine monocytes and neutrophils lacking dipeptidylpeptidase I (DPPI) and therefore lacking active NSPs produced significantly less IL-1β in response to anti-MPO antibodies [77]. Preincubation of human monocytes with cell-permeable serine protease inhibitors or a caspase-1 inhibitor also diminished IL-1β generation. NSPs consist of human neutrophil elastase (HNE), PR3 and cathepsin G (CG). Exogenous PR3 rescued IL-1β generation in DPPI-deficient monocytes. DPPI- and PR3/HNE-deficient myeloid cells as well the IL-1R blocker Anakinra protected from NCGN in an anti-MPO antibody-mediated NCGN mouse model. These findings demonstrate that at least two mechanisms participate in IL-1β generation, namely caspase-1 and PR3, and that PR3 alone or in combination with HNE is important for ANCA-induced NCGN.

Longer differentiation, free of activation signals, might be required for the acquisition of a migratory phenotype in response to later activation; however, such differentiation pattern may not occur in inflamed tissues. Persistent macrophage and DC activation by TLR ligands leads to particularly

powerful inhibitory mechanisms blocking further activation by the same or heterologous stimuli 9. There are several inhibitory factors induced in response to TLR stimulation; it is still unclear, however, how these factors contribute to tolerance for further activation. Some pathways have been connected, like miR146a and IL-10 might both contribute to decreased IRAK1 DNA Synthesis inhibitor expression 11, 21, but the present view supports several coexisting inhibitory pathways in activated DCs and macrophages. Whether these pathways are redundant, additive or synergistic H 89 or act in different conditions or time frames is yet to be understood. Since DCs developing from monocyte precursors in the inflamed tissues might be particularly affected by the constant presence

of microbial compounds and inflammatory mediators, we decided to study which inhibitory pathways are activated in MoDCs in the presence of early and persistent TLR4 stimulation. We set up an assay distinguishing a timely separated role for the different inhibitory molecules and showed that the LPS-induced SOCS1, STAT3, SLAM, miR146a and IL-10 molecules possessed an immediate effect decreasing the activation induced IL-12 production. None of these molecules, however, played an essential role in the establishment of tolerance to further activation signals. The short-term influence of the tested inhibitory signaling components was probably a consequence of the transient increase in their gene expression or the presence of other, more

efficient inhibitory pathways. Although not tested here, it is also possible that certain Ribonucleotide reductase inhibitory factors could modulate the expression of particular genes in DCs, thereby inducing a qualitative tuning of cellular functions. Contrary to these pathways, IRAK-1 downregulation, occurring in MoDCs receiving early activation through TLR4 during differentiation, might alone be sufficient to inhibit further activation through TLR molecules, as demonstrated by the strong inhibitory effect of a siRNA induced IRAK-1 downregulation on IL-12 secretion. Previously, SOCS1 has been implicated in establishing tolerance in MoDCs that developed in the presence of TLR4, TLR2 or TLR3 ligands through inhibiting GM-CSF receptor signaling and thereby preventing DC differentiation 11. A blockade of the DC differentiation pathway as a consequence of TLR stimulation on monocyte precursors has also been indicated by other studies, in case of human MoDCs in vitro 27 and in monocytes entering the skin in response to Gram-negative bacteria 28.

These studies pointed to complex crossregulations between type I and type II IFNs. Here, we investigated side-by-side the role of types I or II IFN pathways in ECM development in response to either hepatic or blood-stage

PbA infection. We confirmed that IFN-γR1−/− mice are fully resistant to ECM after PbA merozoite infection [11, 12] and documented for the first time their absence of brain pathology and LEE011 research buy vascular flow perturbation by MRI/MRA. Further, we extended the study to show ECM resistance of IFN-γR1−/− mice after PbA liver-stage/sporozoite infection. On the other hand, IFNAR1−/− mice showed partial protection or delay in ECM development after PbA sporozoite or merozoite infection. Therefore, we show for the first time that the types I or II IFN pathways are central to ECM development following sporozoite-initiated infection.

Type I IFN pathway was reported to suppress T-cell dependent parasite control during blood-stage PbA infection [21]. Here however, ECM protection was not associated with a decrease in parasitemia or thrombocytopenia in either type I www.selleckchem.com/products/pifithrin-alpha.html or type II IFNR-deficient mice, after hepatic or blood-stage PbA infection. Therefore, our data are not in line with the previous study of Haque et al. [21], which concluded that IFNAR1−/− mice exhibited protection against cerebral malaria associated with reduced parasitemia and increased T-cell mediated

parasite control, but are in agreement with that of Sharma et al. [42] that reported no difference in parasitemia in IFNAR1−/− mice after blood-stage PbA infection. However, protection against cerebral malaria of IFNAR1−/− mice was shown in one survival Masitinib (AB1010) curve in Sharma et al. [42], which is only partial in our hands. Differences in deletion, genetic background or experimental conditions might account for the difference in the extent of protection of the IFNAR−/− mice used. We used mice deficient for IFNAR1 subunit, deleted for exon 3–4, from Muller et al. [43] while Haque et al. [21] used IFNAR1−/− mice deleted for exon 5, from Hwang et al. [44]; Sharma et al. did not mention the origin of the IFNAR1−/− mice they used [42]. Furthermore, the role of type I IFNs in ECM development after sporozoite infection was not addressed in these studies, and we report for the first time the role of type I and type II IFNs in cerebral malaria pathogenesis after sporozoite infection. PbA-associated lung inflammation was unaffected in IFNAR1−/− and IFN-γR1−/− mice, pointing to an effect on ECM adaptive response rather than on systemic parasite control and inflammatory response.

Although liquid media detected fewer strains of Exophiala, Pseudallescheria and Scedosporium species, additional hyphomycete species not detected by other methods were isolated. Current conventional click here methods are insufficient to detect non-Aspergillus hyphomycetes, especially

Exophiala, Pseudallescheria and Scedosporium species, in sputum samples of cystic fibrosis patients. “
“We present a single-centre, retrospective study (1985–2012) of 22 cases of mucormycosis in children. A total of 158 mucormycosis cases were identified, of which 22 (13.96%) were children. The mean age of the children was 10.3 years (range: 6 months–18 years), and 59% of the infections occurred in males. The rhinocerebral form was the main clinical presentation (77.27%), followed by the primary cutaneous and pulmonary patterns. The major underlying predisposing factors were diabetes mellitus in 68.18% of the patients and haematologic diseases in 27.7% of the patients. The cases were diagnosed by mycological tests, with positive cultures in 95.4% of the patients. Rhizopus arrhizus was the foremost aetiologic agent in 13/22 cases (59.1%). In 21 cultures, the aetiologic agents were identified morphologically and by molecular identification. In 10 cultures, the internal transcribed spacer region of the ribosomal DNA was

sequenced. Clinical cure and mycological cure were achieved in 27.3% cases, which were managed with Janus kinase (JAK) amphotericin B deoxycholate and by treatment of the underlying check details conditions. Mucormycosis (formerly zygomycosis), is an invasive fungal infection caused by opportunistic fungi. The main aetiologic agents responsible for mucormycosis were reclassified in the subphylum Mucoromycotina in the order Mucorales.[1-3] The disease is associated with the presence

of underlying conditions, and it is particularly associated with uncontrolled diabetes mellitus (DM) in developing countries, such as Mexico and India.[4, 5] In contrast, in developed countries, mucormycosis is mostly associated with immunocompromised patients, such as those with haematological malignancies (HM) including neutropenia due to leukaemia, hematopoietic stem cell transplantation, and solid organ transplantation. Mucormycosis has also been reported in immunocompetent hosts with skin trauma or burns.[2, 3, 6] Mucormycosis is a cosmopolitan disease. Its aetiological agents are ubiquitous and thermotolerant organisms that usually grow in soil and decaying matter, where they act as contaminant fungi in fruits, vegetables, bread and seeds. The spores are released in the air leading to inhalation or direct inoculation of disrupted skin. Mucormycosis is most commonly caused by the genus Rhizopus, and the disease is less frequently caused by Lichtheimia (formerly Absidia), Rhizomucor, Cunninghamella, Syncephalastrum and other fungi.

On the other hand, RIG-I interacted with V and Vcys but not with P/V, Vu, and Vu cys (Fig. 2B), suggesting that the interaction requires the entire V protein and that cysteine mutations did not affect

the interaction. Similar results were obtained in binding of the V protein with IKKɛ and IRF3 (data not shown). These results show that only MDA5 interacts with the V unique region and that RIG-I, IKKɛ and IRF3 interact with the V protein in a mode different from MDA5. We next investigated whether the V and MDA5 interaction was related to inhibition of IRF3 activation. 293T cells were transfected with an IRF3-dependent reporter plasmid, p-55C1B-EGFP, together with FL-MDA5 and one of the viral proteins. Cells were further GSK1120212 cell line transfected with poly(I:C), and IRF3 transcription activation was investigated. EGFP expression showed that the V protein significantly suppressed IRF3 activation induced by overexpression of FL-MDA5 (Fig. 3A). Expression of EGFP as well as FL-MDA5 JAK inhibitor and a viral protein was confirmed by western blotting (Fig. 3B), and light intensity of EGFP protein bands was quantitated and plotted in a graph (Fig. 3C).

The N-terminal part of the V protein lacking the V unique region (P/V) and the C protein (C) did not suppress IRF3 activation. The V protein with a single point mutation of a cysteine to alanine at the V unique region (Vcys2A: C341A and Vcys7A: C365A) also did not suppress IRF3 activation. Amino acid substitutions of the SeV V protein at those positions ameliorated viral load and pathogenicity in a mouse model (11). Influenza virus NS1 protein (NS1) did not suppress IRF3

activation in this condition. SeV C protein and influenza virus NS1 protein are known to inhibit IRF3 activation and IFN-β production (27, NADPH-cytochrome-c2 reductase 28, 29). The inhibition is thought to be due to reduction of RNA species that belongs to pathogen-associated molecular patterns. These two proteins did not inhibit IRF3 activation induced by overexpression of MDA5 and poly(I:C) treatment. A similar experiment using an IRF3-dependent GFP and luciferase reporter plasmids showed that V and Vu suppressed IRF3 activation and that the Vcys and Vu cys, which have two point mutations at the cysteine residues in the V unique region, and P/V did not suppress the IRF3 activation (Fig. 4). These results indicate that the V protein suppressed MDA5-induced IRF3 activation in a Vu-dependent and cysteine-dependent manner, corresponding to the mode of interaction of V proteins with MDA5. We previously reported SeV V mutants with attenuated pathogenicity (11, 12). SeV V-H318N, R319W, R320G, and W336G were highly attenuated in virulence by more than 25-fold in 50% mouse lethal dose, and SeV V-E321K and P339T were mildly attenuated (12). We infected FL-MDA5-transfected cells with V mutant viruses, and interaction of the V mutant protein with FL-MDA5 was then investigated by immunoprecipitation and western blotting.

However, the prevalence

of subtler forms of neurocognitive dysfunction, which together with HAD are termed HIV-associated neurocognitive disorders (HAND), continues to escalate in the post-cART era. The microgliosis, astrogliosis, dendritic damage, and synaptic and neuronal loss observed in autopsy cases suggest an underlying neuroinflammatory process, due to the neurotoxic factors released by HIV-infected/activated macrophages/microglia in the brain, might underlie the pathogenesis of HAND in the post-cART era. These factors are known to induce the integrated stress response (ISR) in several neurodegenerative diseases; we Fluorouracil purchase have previously shown that BiP, an indicator of general ISR activation, is upregulated in cortical autopsy tissue from HIV-infected patients.

The ISR is composed of three pathways, each with its own initiator protein: PERK, IRE1α and ATF6. Methods: To further elucidate the specific ISR pathways activated in the central nervous system of HAND patients, we examined the protein levels of several ISR proteins, including ATF6, peIF2α and ATF4, in cortical tissue from HIV-infected patients. Results: The ISR does not respond in an all-or-none fashion in HAND, but rather demonstrates a nuanced activation pattern. Specifically, our studies implicate the ATF6 pathway of the ISR as a more likely candidate than the PERK pathway for increases in BiP levels in astrocytes. Conclusion: These findings begin to characterize the nature of the ISR response in HAND and provide potential targets for therapeutic intervention in this disease. “
“Ependymosarcoma EGFR inhibitors list is a new entity of Staurosporine clinical trial malignant gliomas composed of ependymal and sarcomatous components. We report a rare case of ependymosarcoma

with eosinophlic cells which occurred to the right trigon of the lateral ventricle. A 62-year-old man complained of headaches over a 2-month period. A hard, gray mass was found in the right trigon of the lateral ventricle during the operation. Although he received radiation and chemotherapy, the patient died due to tumor disseminating through the whole brain within 7 months after the operation. The histological examination revealed that the anaplastic glial components intermingled with the sarcomatous components. Immunohistochemically, sarcomatous cells were positive for α smooth muscle actin and desmin. However, anaplastic glial cells were not positive for these markers. In addition, Masson trichrome stain showed a plethora of collagen fibers between sarcomatous cells, but no collagen fibers were produced by the glial tumor cells. Solid focal papillary lesions of the glial tumor showed dot-like epithelial membrane antigen and diffuse cytoplasmic D2-40 immunoreactivity. Based on the above findings, these anaplastic glial tumor cells should show focal ependymal differentiation, and sarcomatous cells show myofibroblastic differentiation.

This process can be up- or down-regulated, implying an increased or diminished clearance of alveolar fluid. Studies have demonstrated that net vectorial fluid transport is reduced in human alveolar epithelial cells type II (AEC II) in ALI [23]. Patients suffering from ALI/ARDS most often need to be ventilated mechanically, and therefore remain sedated in intensive see more care units (ICU) [24]. The overall effect of sedatives and anaesthetics – volatile anaesthetics included – on this disease is unclear. As demonstrated previously, the inflammatory response upon endotoxin stimulation in

AEC is partly reversible in the presence of sevoflurane [25]. In an in-vivo model of ALI oxygenation improved in the presence of sevoflurane [26].

However, at the same time volatile anaesthetics are suspected to impair sodium transport [27]. The aim of this work was to investigate the effect of the nowadays commonly used volatile anaesthetic sevoflurane on ENaC and Na+/K+-ATPase in vitro and in vivo. Based on previous in-vitro and in-vivo results with a positive effect of sevoflurane [26], the hypothesis was raised that click here in-vitro activity of ENaC and Na+/K+-ATPase in endotoxin-injured AEC may be increased upon treatment with sevoflurane. Furthermore, an attempt was made to clarify the impact of sevoflurane on oedema in vivo in the endotoxin-induced lung injury model. An improved alveolar fluid clearance upon sevoflurane exposure was postulated. Alveolar epithelial cells type II (AECII).  The

L2 cell line (CCL 149; American Type Culture Collection, Rockville, MD, USA) was derived through cloning of adult female rat lung of AEC type II origin. Cells were cultured in Dulbecco’s modified Eagle’s medium (DMEM; Invitrogen, Carlsbad, CA, USA), supplemented with 10% fetal bovine serum (FBS; Invitrogen), 1% penicillin–streptomycin and 1% 4-(2-hydroxethyl)-1-piperazineethanesulphonic acid buffer (HEPES; Invitrogen). Ribose-5-phosphate isomerase They were grown for 3 days in uncoated plates (Corning Inc., Corning, NY, USA) to >95% confluence. Mixed alveolar epithelial cells (mAEC).  Primary AEC were harvested following an established protocol [28,29]. Briefly, lungs were explanted from male Wistar rats, injected with 10 ml of phosphate-buffered saline (PBS) containing 4 U/ml porcine pancreas elastase (Sigma-Aldrich, Hamburg, Germany) and incubated for 20 min at 37°C. Trachea and large airways were discarded and lungs were minced. Elastase reaction was stopped with 5 ml FBS. After vigorous stirring for 20 min, cells were filtered and incubated for 1 h at 37°C in Petri dishes, coated previously with 1 mg/ml rat immunoglobulin (IgG) (Sigma-Aldrich) in PBS, in order to remove immunocompetent cells. Unattached cells were washed away, and the remaining cells were cultured in DMEM/10% FBS. After a 7-day incubation time, a mixture of type I and type II cells (mAEC) was found (Fig. 1).

The sequence of the complete TG2 gene obtained from the human intestinal epithelial cell line Caco-2 published by us in the National Institutes of Health (NIH) database [4], codifies for a protein of 687 amino acids long. TG2 acts as a monomer and has two closely located binding regions, one for Ca2+ and one for GTP, as TG2 also has GTPase activity. TG2 is expressed ubiquitously and has multiple physiological functions in processes such as blood clotting, wound healing, cell adhesion, cell signalling and apoptosis, among others [1–3]. TG2 has also been associated with pathological conditions, mainly inflammatory diseases click here such as encephalomyelitis and inflammatory myopathies, and neurodegenerative

disorders such as Alzheimer’s, Parkinson’s and Huntington’s diseases, as well as various types of cancer [5–7]. TG2 is involved at different molecular levels in the pathological processes of these disorders, associated mainly with protein cross-linking or deamidation, as well

as regulation of apoptosis. In particular, TG2 plays a critical role in the pathogenesis of coeliac disease (CD), because it is able to deamidate glutamine residues present in toxic proteins from wheat and related cereals. The deamidation of glutamine at selective positions leads to higher-affinity learn more binding of deamidated peptides to human leucocyte antigen (HLA) proteins encoded by the CD predisposing alleles DQ2 (A1*0501, B1*0201) and DQ8 (A1*0301, B1*0302), and also to a higher gliadin-specific T cell stimulation [8–10]. The TG2 gene is regulated by the canonical nuclear factor (NF)-κB pathway in several cell lines, and it has been reported that in cancer and microglial cells TG2 can activate NF-κB

by blocking the inhibitor function of IκBα via polymer formation [11]. Consequently, there is a complex cross-regulation between TG2 activity and the NF-κB pathway, a mechanistic link that can be observed in inflammation and cancer. TG2 expression in human liver cells [12], intestinal epithelial cells [13] and however rat small intestine cells [14] can be induced by proinflammatory cytokines such as interleukin (IL)-1, tumour necrosis factor (TNF)-α and interferon (IFN)-γ, thus amplifying the inflammatory cascade. Therefore, the development of specific TG2 inhibitors with reduced in-vivo toxicity could represent a novel therapeutic approach with the aim of modulating TG2 activity and reduce, or even abolish, the disease processes where the enzyme activity is dysregulated [15]. To this end, more detailed information about the biology and molecular regulation of the TG2 gene in inflammatory settings is needed. In this study, we evaluated the regulation of the TG2 expression by proinflammatory cytokines in different cell lines and particularly in the intestinal mucosa. We found that IFN-γ is the most potent inducer of TG2 expression, and acts synergistically with TNF-α.