All the other data were compared using the Mann–Whitney U-test corrected for multiple comparisons. A P-value of less than 0·05 was considered significant. CTLA-4–Ig was combined with SIT

to examine whether it augments the suppressive effects of SIT in a mouse model of allergic asthma (Fig. 1). OVA-sensitized placebo-treated mice exhibit a strong OVA-specific IgE response, airway eosinophilia and AHR upon OVA inhalation challenges (Fig. 2a–c). OVA-SIT treatment reduced the level of these three basic manifestations of allergic asthma significantly (P < 0·05, Fig. 2a–c), but did not affect significantly the levels of IL-4 and IL-5 in lung tissue (Fig. 2d,e). Co-administration of CTLA-4–Ig with SIT highly augmented the SIT-induced suppression selleckchem of AHR (P < 0·05), OVA-specific IgE (P < 0·005) and airway eosinophilia (P < 0·005) compared to SIT alone. Combination of CTLA-4–Ig with SIT also induced a reduction in the levels of IL-4 (P < 0·05) and IL-5 (P < 0·05) in lung tissue, which was not observed with SIT treatment alone (Fig. 2d,e). Because CTLA-4–Ig has been shown to increase the expression of IDO and thereby induce tolerogenic

effects [31], we tested whether the augmenting effect of CTLA-4–Ig AZD8055 chemical structure on SIT in our model is dependent upon IDO activity. To this aim we compared the effects of co-administration of CTLA-4–Ig with SIT between IDO-KO and wild-type BALB/c mice. OVA-SIT alone suppressed AHR (P < 0·05), specific IgE in serum (P < 0·05) and airway eosinophilia (P < 0·05) in wild-type mice significantly (Fig. 3a,c,d). Co-administration of CTLA-4–Ig with OVA-SIT increased the suppression levels of AHR (P < 0·05),

OVA-specific IgE in serum (P < 0·05) and airway eosinophilia (P < 0·05) significantly, compared to OVA-SIT alone in wild-type mice (Fig. 3a,c,d). In IDO-KO mice, OVA-SIT suppressed airway eosinophilia significantly (P < 0·05), but neither AHR nor specific OVA-specific IgE levels were suppressed (Fig. 3b–d). Surprisingly, co-administration of CTLA-4–Ig with OVA-SIT in IDO-KO mice also strongly enhanced SIT-induced suppression of the manifestation Tideglusib of experimental allergic asthma, resulting in significant suppression of OVA-specific IgE and AHR, which was not achieved by the OVA-SIT alone, and significantly augmented suppression of eosinophils (Fig. 3b–d). These data indicate that although SIT treatment is less efficient in IDO-KO mice, CTLA-4–Ig co-administration remains effective in enhancing the suppressive effects of the OVA-SIT. To evaluate whether administration of CTLA-4–Ig results in the induction of Treg cells, which might suppress reactivation of Th2 cells upon allergen inhalation challenge, we analysed the frequency of CD4+CD25+FoxP3+ Treg cells and CD4+T1ST2+ Th2 cells in peripheral blood 24 h after OVA-SIT. Solo treatment of OVA-SIT alters neither the frequency of CD4+CD25+FoxP3+ Treg cells nor the frequency of CD4+T1ST2+ Th2 cells (Fig. 4a,b).

TSLP is an IL-7-related cytokine mainly expressed by nonhematopoietic cells including epithelial cells and fibroblasts, originally shown to support β-cell development in mice [3, 4]. It was recently shown that TSLP acts on DCs resulting in their activation and induction of a TH2 type immune response [5]. Although sequence homology is weak (43% amino acid sequence identity), human and mice TSLP share similar biological functions [6]. TSLP exerts its activity by binding to a high-affinity heterodimeric receptor that consists of the IL-7 receptor alpha chain (IL-7Rα) and the TSLP receptor (TSLPR) chain and transmits signals via STAT5 activation [7-9]. TSLPR alone

has low affinity for TSLP but together with IL-7Rα forms a high-affinity binding site for TSLP [8, 10]. It has been shown that the interaction TSLP-TSLPR is essential for promoting immune responses against PCI-32765 the intestinal nematode pathogen Trichuris [11,

12]. TSLP is expressed at several mucosal surfaces such as skin, lungs, thymus, and gut, but most of the studies focused on its functions in allergic diseases such as asthma and skin atopic dermatitis where a positive correlation between increased TSLP expression and the aggravation of atopic dermatitis and lung inflammation has been shown [13, 14]. Previous works showed that TSLP expression is upregulated following exposure CHIR-99021 purchase to different factors including inflammatory mediators,

TLR activation and/or tissue damage by a NF-κB dependent mechanism [15, 16]. In addition, it has been demonstrated that the MAPK pathway is also involved in the regulation of TSLP expression in response to IL-1 and PMA-mediated signaling [17, 18]. This infers that both NF-κB and MAPK pathways cooperate in regulating TSLP expression. The role of TSLP in the gut is less extensively studied. Thus far, it has been shown that TSLP is constitutively expressed IMP dehydrogenase in IECs from healthy subjects, where it inhibits IL-12 production by DCs in response to bacteria, but not in cells from patients with chronic inflammation caused by active Crohn’s disease [5]. The aim of this work was to investigate the transcriptional regulation of the TSLP gene in the gut using IEC lines, HT-29, and Caco-2. We examined a 4 kb region of the human TSLP promoter and identified a number of putative NF-κB and AP-1 binding sites. We demonstrated that the NF-κB site located at –370 bp from the ATG (isoform 1) is the key site for IL-1-mediated transcriptional activation of TSLP in the IECs. Further analysis of other epithelial cell models (A549, HEK293, HeLa) confirmed the absolute requirement of this proximal NF-κB binding site for the NF-κB-dependent activation of TSLP gene transcription in epithelial cells. This work has revealed an important cell-specific aspect in the regulation of TSLP in epithelial cells.

Major histocompatibility complex (MHC) class-I H-2kd-restricted cognate antigenic peptides islet-specific glucose-6-phosphatase

catalytic subunit-related protein (IGRP206–214) (VYLKTNVFL) and its mimotopes NRP (KYNKANWFL; agonist), NRP-V7 (KYNKANVFL; super agonist) and TUM (KYQAVTTTL; non-agonist) Selleckchem JNK inhibitor were custom synthesized by Genscript (Piscataway, NJ, USA). Expression of cell surface markers was evaluated by flow cytometry using fluorescence activated cell sorter (FACS)Canto flow cytometer (Becton Dickinson Flow Cytometry Systems, San Jose, CA, USA) and the data were analysed using FlowJo software (Tree Star Inc., Ashland, OR, USA). Total lymph node cells (2 × 105 cells) or purified CD8+ T cells (2·5 × 104 cells) were cultured in 96-well culture plates with the indicated peptides using irradiated splenocytes as antigen-presenting cells (APCs)

(1 × 105 cells) or with anti-CD3/CD28-coated beads for 72 h. Cell proliferation was measured by [3H]-thymidine incorporation [34]. To measure antigen-induced proliferation in vivo, 8.3 CD8+ T cells were labelled with Ibrutinib in vivo carboxyfluorescein diacetate succinimidyl ester (CFSE), as described previously [35], and injected intravenously. Bone marrow-derived dendritic cells (BMDCs) cultured with granulocyte–macrophage colony-stimulating factor (GM-CSF) and IL-4 were pulsed with IGRP206–214 or the control peptide TUM for 1 h at 37°C, washed, resuspended in phosphate-buffered saline (PBS) and injected

subcutaneously in hind footpads. Donor cells recovered from the draining inguinal lymph node were evaluated to measure proliferation. CTL activity was measured using RMA-S-Kd target cells loaded with the cognate peptide, as described previously [1, 32]. The amount of IL-2 in the culture supernatants was determined by sandwich ELISA using antibody pairs purchased from BD Pharmingen Biosciences (Palo Alto, CA, USA). Onset of T1D was monitored by measuring urine glucose levels using Keto-Diastix (Bayer, Canada). Idelalisib Animals with two consecutive readings of >3 were considered diabetic. At the time of euthanasia, pancreatic tissues were processed for histopathology analysis. At least three non-overlapping (200 μm apart) 5-μm sections were evaluated for insulitis [32]. Cumulative incidence of T1D was analysed using Prism software (GraphPad Software Inc., La Jolla, CA, USA). For diabetes incidence, significance was calculated using log-rank (Mantel–Cox) test. For all other parameters, statistical significance was calculated by Student’s t-test. The 8.3-NOD mouse expresses a highly pathogenic, MHC class I-restricted, transgenic 8.3 TCR specific to a peptide derived from the IGRP206–214 [33, 36]. In these mice, the 8.3 TCR transgenic CD8+ T cells (8.3 T cells) infiltrate pancreatic islets from 3 weeks of age [33]. Female 8.

Microsurgery, 2011. “
“Introduction: Microsurgical lower extremity flap reconstruction provides a valuable option for soft tissue reconstruction in comorbid patients. Limb salvage with flap reconstruction can result in limb length preservation. Despite this, few Selleck AZD2281 studies have examined the impact of salvage on patient-centered metrics in this cohort of patients. Therefore, we investigated quality of life and patient satisfaction following microsurgical

lower extremity reconstruction in this high-risk patient population. Factors that resulted in improved patient-centered outcomes were also identified. Methods: A retrospective review was conducted of all patients who had lower R788 supplier extremity free flap reconstruction (FFR) following lower extremity wounds. High-risk patients were identified as having multiple comorbidities and chronic wounds. Patients with traumatic wounds were excluded from analysis. Quality of life was evaluated with the Short Form-12 (SF-12) validated survey. Phone interviews were conducted for survey evaluations. Results: From 2005 to 2010, 57 patients had lower extremity flap reconstruction that met the inclusion criteria. Average follow-up was 236.6 weeks (range, 111–461). Comorbidities included diabetes (36%),

PVD (24.6%), and ESRD (7%). Limb length preservation and ambulation occurred in 82.5% (47/57). Revisional surgery occurred in 33.3% (19/57). Survey response rate was 63%. Average SF-12 PCS and MCS scores were 44.9 and 59.8 for patients able to achieve ambulation and 27.6 and 61.2 for nonambulatory patients. Conclusions: Microsurgical flap reconstruction is a valuable reconstructive

option in high-risk patients. Quality of life is comparable with Cell press a normalized population if limb salvage is successful. Quality of life is decreased significantly when failure to ambulate occurs in this patient cohort. © 2013 Wiley Periodicals, Inc. Microsurgery 34:1–4, 2014. Lower extremity reconstruction with the aim toward limb salvage in the co-morbid patient population is a difficult undertaking for the reconstructive surgeon. Co-morbidities such as diabetes mellitus, peripheral vascular disease, and renal failure add complexity to microsurgical reconstruction. Systemic vascular changes such as recipient vessel disease, recipient site scarring, and donor vessel disease may pose a technical challenge. However, successful outcomes in lower extremity reconstruction are well demonstrated in this patient population and provide patients with the option of limb salvage.[1, 2] Early successful outcomes are predicated by overcoming compromised vascular inflow and by controlling infection. Following the early postoperative period, achieving successful long-term outcomes becomes more challenging. Traditionally flap survival was the marker for defining a successful outcome.

Twenty percent experienced worse symptoms during pregnancy with 53% happening in the third stage of pregnancy. Forty-two percent of the female patients had no pain during or after sexual intercourse, while 34%

experienced occasional pain and 24% had frequent pain. The location of post-sexual pain was lower abdomen (29%), vagina (30%), and back (3%). Twenty-nine percent of the female patients experienced flare-up symptoms related to their menstrual cycle. Twenty-six percent had frequency flare-up related to menstrual cycle, with 66% before menstrual cycle, 26% during menstrual cycle, and 8% after menstrual cycle. Fourteen percent of the female patients experienced DAPT concentration flare up of pain related to the menstrual cycle, with 73% before, 17% during, and 10% after menstrual cycle. The most frequently encountered problems indicated from the studied group were long travel (83%) and sleep (80%), working at position which patients were qualified to do (66%), short travel (58%), partner relationship (35%), family relationships and p38 MAPK inhibitor review responsibilities (24%) (Table 5). Comparing our data with the data analyzed in some large-scale research outside Taiwan, we have the

following findings: The average age in the present study is the same as the age shown in ICDB, but is younger than that offered in the studies of Koziol et al.[12] This suggests that the average age of IC patients through clinical diagnosis has become younger with the increasing awareness of this disease in the field of medicine. Our patients reported that their first symptom occurred at the age of 38, but they did not get diagnosed until the age of 46. Thus, there is a difference of 8 years and it suggests that IC is not a disease that can be diagnosed at the early stage. Compared with the difference of 4–7 years documented in the studies outside Taiwan, the difference of 8 years in the present study implies that the understanding of IC in Taiwan is still not sufficient. In addition, the duration of frequency and urgency symptoms is longer than that

of pain symptoms (i.e. 62 months vs. 46 months). It might imply that the initial symptom of IC patients includes frequency and urgency, accompanied by the symptom of pain. Suffering from pain is then the Flavopiridol (Alvocidib) biggest factor that causes IC patients to become serious about clinical and medical assistance. Some research studies have found that patients who suffer from early symptoms are younger than patients who suffer from typical IC patients. Variability and progression is commonly seen in interstitial cystitis. Because typical symptoms such as frequency, urgency, pain, and nocturia might not occur simultaneously, the biggest challenge that clinicians encounter is how to diagnose the disease at the early stage and how to treat patients appropriately. We can tell the difference between chronic prostatitis and interstitial cystitis more precisely at present day..

2b). The Sommer’s sectors of hippocampi bilaterally exhibited brownish discoloration (Fig. 2b). The superior temporal gyri were relatively spared compared with the middle and inferior temporal gyri (Fig. 2b). The substantia nigra and locus ceruleus were depigmented. Histopathological examination revealed marked neuronal loss and gliosis

in widespread areas, including the frontal and temporal Trichostatin A price cortices, hippocampi and parahippocampal regions, amygdala, thalamus, hypothalamus, midbrain and cerebellar cortex. Degeneration was advanced to form laminar necrosis-like changes in the middle layers of the frontal and temporal cortices (Fig. 3a). Numerous swollen storage neurons were present throughout the CNS (Fig. 3b). NFTs were frequently found in the CNS regions where neuronal loss and gliosis were prominent, such as the frontal and temporal cortices, hippocampus, amygdala, hypothalamus, basal ganglia, thalamus, brainstem and spinal cord (Fig. 3c,d). These findings strongly suggested the diagnosis of NPC. Histopathological

findings outside the CNS included the occurrence of lipid-laden foamy macrophages in the bone marrow, spleen (Fig. 4a), liver (Fig. 4b) and lung. Filipin staining of the liver sections revealed that Kupffer cells (sinusoidal macrophages) accumulated intracellular free cholesterol (Fig. 4c). Ultrastructural examination revealed accumulation of electron-dense materials in liver macrophages Vincristine molecular weight (Fig. 5a) and membrane-bound oligolamellar inclusions typical of NPC in the occipital cortex (Fig. 5b,

arrows). In addition to the above-mentioned findings, which have been well recognized as characteristic of NPC, LBs were observed in many CNS regions. Thalidomide In HE-stained sections, LBs presented as eosinophilic hyaline masses against a background of accumulated lipids in swollen storage neurons (Fig. 6a,b). Cortical LBs were also found in some neurons with minimal lipid storage (Fig. 6c). LBs were distributed mainly in deeper layers of the cortices of the frontal and temporal lobes, especially the anterior cingulate cortex, as well as the subiculum, amygdala, basal forebrain, hypothalamus, substantia nigra, oculomotor nucleus, superior colliculus, locus ceruleus, inferior olivary nucleus, and dorsal motor nucleus of the vagus nerve. LBs were immunohistochemically stained for α-synuclein and ubiquitin, as well as for HDAC6 and p62/SQSTM1, both of which are known to localize in LBs of Parkinson’s disease and dementia with LBs (Fig. 6d–g).[10, 11] The distribution of swollen storage neurons, NFTs and LBs is summarized in Table 1. Immunohistochemical staining with anti-ApoE4 antibody revealed no immunoreactivity in the brain, suggesting that this patient did not have the ApoE ε4 allele (data not shown).

In contrast, when PBMCs from newly diagnosed, MAPK Inhibitor Library high throughput relapsed and chronic TB were stimulated in vitro with PPD

or H37Ra, they produced more granulysin than did stimulated controls, a finding which is in contrast to the median and individual concentrations of circulating granulysin. Possible explanations for this discrepancy are that: (i) during in vivo stimulation during active disease, granulysin might be rapidly consumed because of the ongoing effector immune response; (ii) in vivo serum granulysin is reduced during active disease because of a reduction in the T cell subset dedicated to its production (15); or (iii) when PBMCs that possibly contain primed T cells (indicated by high plasma concentrations of granulysin) are re-stimulated in vitro with either PPD and H37Ra, they may produce more granulysin in the supernatant. A related phenomenon has been reported in which stimulation with PPD in vitro PBMCs from healthy tuberculin skin test positive individuals results in increased granulysin expression in PPD-stimulated CD4+ and CD8+ T cells, compared to that of unstimulated cells (20). Moreover, it has been reported that, after stimulation in vitro with Mtb including H37Ra, both CD4+ and CD8+ T cells up-regulate mRNA expression for granulysin,

granzyme A and B, perforin and CD95L (Fas ligand), and are able to lyse Mtb infected target cells, this being mediated primarily through the granule exocytosis pathway (21). Median and individual concentrations Selleckchem Everolimus of circulating IFN-γ in patients with newly diagnosed Carnitine dehydrogenase and relapsed TB were significantly higher than in healthy controls. Similar results, namely greater IFN-γ production than in stimulated healthy controls, were seen with in vitro stimulation with PPD and H37Ra of PBMCs from most patients with newly diagnosed and half of relapsed TB patients, although some

stimulated PBMCs from these patients produced less IFN-γ. However, the median IFN-γ production with in vitro stimulation of PBMCs from relapsed TB patients is lower than that of healthy controls. Surprisingly, PBMCs from healthy individuals stimulated in vitro with PPD and H37Ra in this study did induce significant IFN-γ production. However, these four healthy individuals were recruited from the Blood Bank of a provincial hospital in Chiang Rai where TB is endemic, and did not undergo chest X-ray, TST and any testing for latent TB infection and infection manifesting as active TB by IGRAs. At the time of recruitment, based on their histories, these individuals were thought to be healthy blood donors. However, we cannot be sure that they had never been exposed to Mtb and remained asymptomatic, or been vaccinated with BCG. It is known that 5–10% of those infected with Mtb will progress towards active TB during their lifetime, whereas the remainder are resistant to active TB, but remain infected.

Measles virus replication in human TEC in vitro results in terminal differentiation and apoptosis [47]. Surprisingly, with regard to thymic output, an increase in TREC+ CD4+ T cells has been reported in measles virus-infected children despite severe lymphopenia [48]. Infections with CMV (belonging to the Herpesviridae family) are also immunosuppressive, resulting in poor cellular

responses from cultured blood leucocytes, low CD4/CD8 ratios and potential secondary infections [49]. At the thymic level, CMV infection in the SCID-Hu mouse results in high and PKC412 clinical trial persistent viral replication in the thymus. The majority of virus-infected cells were localized in the thymic medulla and immunofluorescence analysis Lapatinib mouse identified TEC rather than any haematopoietic cell population as the principal hosts for viral replication [50]. Infection of BALB/c mice with murine (M)CMV decreased the numbers of cells recovered from the thymus by 80–90% after 4–7 days, although fewer than 0·001% were infected productively with the virus. A loss of cortical thymocytes was evident in histological sections and correlated with depletion of CD4+CD8+ cells [51]. Suppression of cell-mediated immunity is also a common feature of rabies virus

infection [52,53]. This phenomenon relies essentially upon thymocyte apoptosis and thymus atrophy (despite no evidence of virus infection), as observed in numerous studies carried out in

mice [52,54–56]. Altogether, these data show that viruses belonging to various families can infect the thymus in vivo and in vitro. Clearly, viruses can impair thymus functions significantly. Like any autoimmune disease, T1D results from self-tolerance breakdown. Self-tolerance establishment is initiated at the central level within the thymus. Thus, it cannot be excluded that disturbance in thymic architecture and/or function may play a role in the development of autoimmune processes. At the peripheral level, self-tolerance is based on regulatory T cells (Treg), a specialized subset of T cells whose functions include the suppression of autoreactive T cells. In the case of T1D, pancreatic islet β cells are targeted selectively by the autoimmune destruction process, meaning that Docetaxel order there is a defect in the recognition of islet β cell antigens. Anomalies in Treg cells functions and numbers have been associated with autoimmunity towards islet β cells and are thought to play a role in the progression of T1D [57]. At the thymic level, this defect can arise from several aberrations encountered during T cell education through positive and negative selection. During positive selection, the newly rearranged TCRs expressed on developing thymocytes interact with MHC molecules on cortical TEC; thus, any anomaly in MHC and/or TEC may lead to aberrant positive selection.

The secretion of IL-17 was above the detection limit of the assay in eight of 23 intestinal biopsy samples from CD patients, but in none of five reference samples. We examined the apoptotic effects of IL-17 on Caco2-cells in vitro, alone or in combination with TNF-α, which is known to be apoptotic for epithelial cells. IL-17 receptor A mRNA transcripts were highly expressed in CaCo-2 cells (Ct was 24 for IL-17RA and 13 for 18S; n = 8). Furthermore,

incubation with IL-17 increased the transcription of the anti-apoptotic gene bcl-2 but did not up-regulate the expression of BAX, which is activated in the apoptosis (Fig. 4). We did not find evidence supporting an up-regulation of intestinal IL-17 immunity in T1D-related intestinal inflammation or in potential CD, but in CD the IL-17 response was linked to untreated CD characterized find more by villous atrophy and IL-17

immunity was down-regulated after GFD. Our results check details point out that up-regulation of mucosal IL-17 immunity is seen at the late stage of CD, when villous atrophy has developed. We found up-regulation of IL-17 immunity only in children with untreated CD, as demonstrated in independent patient series from Finland and Sweden. Elevation of duodenal IL-17A transcripts was observed and the small intestinal biopsies of untreated CD patients seemed to spontaneously secrete more IL-17A in vitro compared to reference children. However, the numbers of IL-17-positive cells in Finnish children with untreated CD were not increased significantly compared to reference children. This might indicate up-regulation of Il-17A production without remarkable expansion of Th17 cells at the time of villous atrophy. Our findings of the effect of GFD on the normalization of intestinal IL-17 up-regulation is in agreement with Italian studies showing an association of mucosal IL-17 activation in untreated but not in GFD-treated CD [23,24]. We also studied healthy children with and many without

TGA, and showed that up-regulation of IL-17 immunity does not occur in children with TGA, who are at high risk of CD and are considered as having potential CD. In potential CD the inflamed intestinal mucosa is characterized by increased numbers of γ/δ T cells and up-regulation of the IFN-γ pathway. Accordingly, our findings in children with potential CD indicate that wheat gliadin induced mucosal inflammation, which is already present in potential CD, does not include IL-17 immunity. Our findings of the activation of IL-17 immunity at only a late stage of the disease could explain the discrepant reports of IL-17 secretion by gliadin-specific T cells [12,25]. Bodd et al. showed that T cells reactive to deamidated gliadin do not secrete IL-17 [12]. A recent study, however, reported that gliadin-specific Th17 cells are present in the mucosa of untreated CD patients [25].

325; P = 0.034) (Fig. 3). In addition, the glomerular expressions of miR-146a correlated with both estimated GFR (r = 0.453; P = 0.028) and histological activity

index (r = 0.494; P = 0.027) selleck compound (Fig. 4). The glomerular or tubulointerstitial expressions of miR-155 did not correlate any clinical or histological parameter of lupus activity (details not shown). We further explored the relation between intrarenal miRNA level and gene expression of TWEAK, Fn14, IP10 and CXCR3, which we reported previously on this group of patients.16 In short, glomerular expression of Fn14 correlated with that of miR-146a (r = 0.424, P = 0.028), while tubulointerstitial expression of Fn14 correlated with that of miR-155 (r = 0.401, P = 0.017). Similarly, tubulointerstitial expression of CXCR3 correlated with that of miR-146a (r = 0.437, P = 0.037). The result is this website summarized in Figure 5. In the present study, we found that intra-renal expression of miR-638, miR-198 and miR-146a are differentially expressed between patients with lupus nephritis and normal controls. Furthermore, the degree of change in miRNA expression correlated with clinical disease severity. The results suggested that these miRNA species may play a role in the pathogenesis of lupus nephritis. Our result is, by and large, consistent with previous studies.

For example, Te et al.9 reported that miR-638 was upregulated in the PBMC of SLE patients, while we found a paradoxical change in its intra-renal expression: downregulated in glomerulus but upregulated in the tubulointerstitium. It should be noted, however, that it was the tubulointerstitial miR-638 that contributed more to the overall expression and correlated with functional parameters (proteinuria and SLEDAI score; see Fig. 2). In the same study, miR-198 was found to be upregulated in the PBMC cell out lines derived from SLE patients,9 which is also in line with our observation. Our previous study found that, as compared with normal controls, SLE patients had a lower serum level, but higher urinary level, of miR-146a.12 The result of our present study supports the hypothesis of a parallel change

between intra-renal and urinary miRNA level. Unfortunately, we do not have concurrent urine samples of our patients for comparison. Our data also suggest a regulatory role of miR146a and miR155 in the expression of inflammatory genes such as CXCR3 and Fn14. It should be emphasized that the causal relationship between studied miRNAs and the pathogenesis of LN remains to be elucidated. Nonetheless, there is emerging evidence that the biological effects of several miRNA species are mediated via the TWEAK/Fn14 axis. For example, the expression of miR-146a in C2C12 myotubes significantly increased in response to TWEAK treatment.22 In our study, the glomerular expression of miR-146a was also found to correlate with that of Fn14, that is, the receptor of TWEAK.