Autoimmune

thyroiditis, or Graves’ disease, is due to increased infiltration of lymphocytes into the thyroid where they recognize the thyroid stimulating hormone receptor; this leads to autoantibody production, tissue necrosis and loss of thyroid function. The importance of CD40 signalling in Graves’ disease was recognized after the discovery that CD40 is present on thyroid epithelial Selleckchem ZVADFMK cells [54], where it interacts with CD40L (CD154)-expressing autoreactive T cells. In agreement with this observation, blockade of the CD40–CD40L interaction with anti-CD40L antibodies has been shown to prevent experimental thyroiditis [55]. Type 1 diabetes, or insulin-dependent diabetes, is caused by autoreactive T cells that recognize antigens such as insulin and glutamic acid decarboxylase selleckchem on B cells

in the islets of Langerhans. B cells also play important roles in disease pathogenesis, as revealed by B cell-deficient NOD mice [56] and treatment of NOD mice with CD40L antibodies [57]. As the CD40 signal is critical for antibody production and Ig class-switching, depletion of CD40+ B cells, or deletion of endogenous B cells, lowers autoantibody production in these mice and decreases disease severity. In addition to CD40+ B, CD40+ T cells are important in the induction of diabetes in NOD mice [58]. The importance of CD40–CD40L has also been underscored in collagen-induced arthritis (CIA). Treatment of mice with collagen type II and anti-CD40L antibodies blocked joint inflammation, serum antibody titres to collagen, synovial infiltrates and erosion of cartilage and bone [59]. Also, when treated with anti-CD40L antibodies, lupus-prone mice showed reduced glomerulonephritis [60]. Similarly, in an open-label study in SLE patients treated with anti-CD40L, humanized mAb exhibited

disease alleviation, including reduced anti-ds-DNA titres [61,62]. Blockade of CD40–CD40L interaction by anti-CD40L antibodies reduced the incidence and severity of T helper type 1 (Th1)-mediated experimental autoimmune uveoretinitis (EAU) in susceptible B10.RIII mice immunized with autoantigen interphotoreceptor retinoid binding protein (IRBP) in complete Freund’s adjuvant (CFA) [63]. Further analysis revealed that in anti-CD40L Clomifene antibody-treated mice innate responses to autoantigen IRBP were reduced significantly, but no Th2 dominance was observed [63]. The alleviation of EAE and MS by anti-CD40L therapy [64] further signifies the importance of CD40–CD40L axis in autoimmune diseases (Table 1, Fig. 1c). CD134 (OX40), an inducible T cell co-stimulatory molecule, is one of the most extensively studied members of the TNF superfamily. OX40 expression is activation-induced and, once expressed, OX40 binds OX40L (CD134L) present on a variety of cells [65–67]. OX40 signalling promotes T cell activation, induction of cell survival genes and production of cytokines [68]. OX40 signals play crucial roles in autoimmune and viral diseases, cancer and transplantation [68].

It is also designated as cluster of differentiation 281 (CD281). It is expressed at higher levels in the spleen and peripheral blood cells [36]. Human TLR1 plays an important role in host defence against M. tb. A study in Seattle and Vietnam population identified seventeen polymorphisms in the coding region, in which seven variants

were synonymous C114T (H38H), A914T (H305L), C944T (P315L), T1583C (C528C), G1677A (P559P), T1760G (V587G), T1892G (L631R), and ten were non-synonymous G1968A (L656L), C2198T (P733L), T130C (S44P), A1482G (V494V), C1938T (H646H), G239C (R80T), C352T (H118Y), A743G (N248S), A1518G (S506S) and T1805G (I602S),with seven of them in the extracellular domain and two in the intracellular domain [37]. TLR1/2 and TLR2/6 receptor pairs exhibit different specificities towards

many microbial agonists Ibrutinib supplier [38-40], which is determined by the region composed of LRR motifs. Recently, a study reported that there are three nSNPs located in the LRR region of TLR1. P315L is one of the nSNPs that may have impact on the innate immune response and clinical susceptibility to many infectious diseases [41]. Studies have shown that TLR1 polymorphisms were associated with impaired cell-surface expression [42]. R80T, N248S and I602S nSNPs were associated with invasive aspergillosis [43] and with Crohn’s disease [44]. In malaria and H. pylori-induced gastric diseases, 602S was found to be a risk factor [45, 46]. A study reported in Germany found that the 743A and 1805G correlate with TLR1 deficiency and impaired Y-27632 in vitro functionality and were strongly associated with susceptibility to TB [42]; similarly, in African American and European American patients, common

variants like N248S and S602I and rare variants like H305L and P315L were associated with altered immune response to M.tb ligands and susceptibility to Leprosy [47]. In response to stimulation with the TLR1 ligand PAM3, the variants Cyclic nucleotide phosphodiesterase containing 602I were fully capable of mediating NF-kB signalling, while variants with SNP 602S had impaired signalling, this implies that 602I regulates lipopeptide responses. N248 (common in European Americans) is a conserved amino acid site in the extracellular domain of TLR1 and is a putative glycosylation site. Replacement of the Asn residue with Ser might result in altered glycosylation, potentially changing TLR1 folding or function [47] (Table 1). N248S G743A (rs4833095) I602S T1805G (rs5743618) H305L A1188T (rs3923647) P315L A945G (rs5743613) R677W no rs designation available R753Q (rs5743708) 2258G/A T399I C+1196T (rs 4986791) D299G A+896G (rs 4986790) +1083C/G T 361T (rs3821985) +745 T/C S249P (rs5743810) 129 C/G (rs3764879) 2167 A/G (rs3788935) 1145 A/G (rs3761624) +1A/G Met1Val (rs3764880) G+1174A rs352139 TLR2 is encoded by a DNA sequence composed of 2352 bases that codes for 784 amino acids [48].

We thank the staff of the Fetal Medicine Unit and the midwives at St. George’s Hospital, and all the patients for their assistance with this study. RD recruited all subjects and together with PN conducted the observations, and maintained the database. RR

helped in the analysis and wrote the first draft with RD. DW performed the statistical analysis. All authors discussed click here the results and implications and commented on the manuscript at all stages. None. None. “
“Please cite this paper as: Wang F, Hu Q, Chen C-H , Xu X-S, Zhou C-M, Zhao Y-F, Hu B-H, Chang X, Huang P, Yang L, Liu Y-Y, Wang C-S, Fan J-Y, Zhang K, Li G-Y, Wang J-H, Han J-Y. The protective effect of cerebralcare granule® on brain edema, cerebral microcirculatory disturbance and neuron injury in a focal cerebral ischemia rat model. Microcirculation 19: 260–272, 2012. Objective:  The purpose of the present study was to explore the protective effects of CG on rat cerebral injury after focal cerebral I /R. Methods:  Male Sprague–Dawley rats were subjected to right middle cerebral artery occlusion for 60 minutes followed by reperfusion for 60 minutes or 24 hours. CG (0.4 or 0.8 g/kg) was administrated 90 minutes before ischemia. Brian edema was evaluated selleckchem by Evan’s blue dye extravasations and brain water content, leukocyte adhesion, and albumin leakage were determined with an upright fluorescence microscope, and neuron damage was assessed by 2,3,5-triphenyltetrazolium

Glycogen branching enzyme chloride staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and immunohistochemistry of caspase-3, p53, p53 upregulated modulator of apoptosis. Results:  Focal cerebral I/R elicited a prominent brain edema, an increase in leukocyte adhesion, and albumin leakage, as well as neuron damage. All the insults after focal cerebral I/R were significantly attenuated by pretreatment with CG. Conclusions:  Pretreatment with CG significantly reduced focal cerebral I/R-induced

brain edema, cerebral microcirculatory disturbance, and neuron damage, suggesting the potential of CG as a prophylactic strategy for patients in danger of stroke. “
“Compromised perfusion of the capillary bed can lead to organ failure and mortality in sepsis. We have reported that intravenous injection of ascorbate inhibits platelet adhesion and plugging in septic capillaries. In this study, we hypothesized that ascorbate reduces aggregation of platelets and their surface expression of P-selectin (a key adhesion molecule) in mice. Platelets were isolated from control mice and subjected to agents known to be released into the bloodstream during sepsis (thrombin, ADP or U46619, thromboxane A2 analog). Platelet aggregation was analyzed by aggregometry and P-selectin expression by flow cytometry. Platelet-activating agents increased aggregation and P-selectin expression. Ascorbate inhibited these increases. This inhibitory effect was NOS-independent (LNAME had no effect).

Under Th17 conditions, the binding of Mel-18 at the Ifng promoter was much lower than at the Il17a promoter (Fig. 4H). We did not notice changes in the binding activity of Mel-18 at Hoxa7 promoter in the presence or absence of Th17 polarizing cytokines (Fig. 4G). As with Mel-18, there were no significant changes JAK inhibitor in the expression levels of the mRNA or protein of Ezh2 if the restimulation was either in the presence of Th17 conditions or IL-12 (Fig. 5A and B). But in contrast to Mel-18, the binding activity of Ezh2 at the Il17a promoter was not decreased without cytokines (Fig. 5C). The binding of Ezh2 at the Rorc,

Ifng, Tbx21 and Hoxa7 promoters was also not significantly altered between the different conditions (Fig. 5D–G). Ezh2 was associated more strongly with the Il17a promoter than with the Ifng promoter (Fig. 5H), but the differences were smaller in comparison to the differential binding activity of Mel-18 at these promoters (Fig. 4H). To determine whether the signaling pathways downstream to TGF-β were sufficient to maintain the high level of the binding activity of Mel-18 at the Il17a promoter, Th17 cells were restimulated

without cytokines or in the presence of either TGF-β alone or combination of TGF-β, IL-6 and IL-23 (Fig. 6A). The binding of Mel-18 was only modestly decreased when the restimulation was in the presence RAD001 mw of TGF-β alone than with the cytokine combination. When the cells were restimulated without cytokines, the binding was further reduced almost to the level of unstimulated cells (resting). These results show that TGF-β is required for the maintenance of the binding activity of Mel-18 at the Il17a promoter

beyond the early TCR-dependent stage. Nevertheless, the presence of TGF-β in the absence of TCR stimulation, as in the resting conditions, is insufficient to induce the binding activity of Mel-18 at the Il17a Non-specific serine/threonine protein kinase promoter. The binding activity of RORγt was correlated with this of Mel-18; RORγt was associated with the Il17a promoter when the Th17 cells were restimulated for 18 h in the presence of the Th17 polarizing cytokines but not in their absence (Fig. 6B). The decrease in the binding activity of RORγt may reflect the reduced expression of Rorc mRNA following restimulation without TGF-β (Fig. 3A). However, we did not recognize substantial changes in the expression levels of RORγt protein at this time point (Fig. 6C). Therefore, as early as 18 h following restimulation the recruitment of RORγt, and not its expression, is regulated by the polarizing cytokines.

Clinical trials in the general population have shown that lifestyle modifications are fundamental to blood pressure control. Weight reduction,10,11 increasing physical activity,12,13 consuming a diet that is low in fat and rich in plant-based foods,12 reducing R428 mw dietary sodium intake13,14 and reducing excessive alcohol intake15,16 lead to reductions

in blood pressure and can enhance the efficacy of antihypertensive medications. Many countries have produced guidelines for the management of hypertension in the general population, all of which incorporate nutritional recommendations.17–19 This review set out to explore and collate the evidence for the safety and efficacy of specific nutrition interventions for the prevention and management of hypertension in kidney transplant recipients, based on the best evidence up to and including September 2006. Relevant reviews and studies were obtained from click here the sources below and reference lists of nephrology textbooks, review articles and relevant trials were also used to locate studies. Searches were limited to studies on humans; adult kidney transplant recipients; single organ transplants and to studies published in English. Unpublished studies were not reviewed. Databases searched: MeSH terms and text words for kidney transplantation were combined with MeSH terms and text words for both

hypertension and dietary interventions. MEDLINE – 1966 to week 1, September 2006; EMBASE – 1980 to week, 1 September 2006; the P-type ATPase Cochrane Renal Group Specialised Register of Randomised Controlled Trials. Date of searches: 22 September 2006. There are few published studies on the nutritional management of hypertension in kidney transplant recipients. Level I/II: There are no randomized controlled trials investigating the efficacy of nutritional interventions for treating hypertension in adult kidney transplant recipients. Level III: There is one pseudo-randomized

controlled study examining the efficacy of a sodium-restricted diet20 and one non-randomized prospective study, which compared the efficacy of a dietary sodium restriction in patients treated with cyclosporine and those treated with azathioprine.20 There is one randomized crossover study21 examining the effect of L-arginine supplementation on blood pressure in kidney transplant recipients. Level IV: Cross-sectional studies22,23 are of poor quality. In a pseudo-randomized study, Keven et al.24 investigated the effect of a sodium restriction on blood pressure levels. Thirty-two kidney transplant recipients with stable kidney function were randomly assigned to either the intervention group, who followed a 3-month sodium-restricted diet (80–100 mmol/day), arranged by a dietitian, or to the control group.

Act1−/−, TCRβ/δ−/−, and TKO mice (IgG and IgM containing IC, respectively)

were not sufficient or of the correct type to attract and fixate complement. It should be noted that this was not due to the relatively young age (20 weeks) of the mice, as staining of kidneys from 8–12 month-old B6.Act1−/− and TKO mice also failed to show glomerular C3 fixation (data not shown). Also, this observation correlates with the fact that none of the mice (up to 12 months of age) developed renal failure as determined by elevated proteinuria levels (data not shown). In addition to developing lupus-like disease, BALB/C.Act1−/− mice develop early and severe SjS-like disease [8]. In contrast, B6.Act1−/− mice failed to develop gross signs of SjS-like disease including enlarged submaxillary glands and elevated serum anti-SSB/La IgG autoantibodies (Fig. 4A–B). We LY2109761 supplier did find occasional IgG deposition within the glands of B6.Act1−/− mice which appeared to be diminished

in the absence of T cells, however both WT and B6.Act1−/− mice displayed areas of mononuclear cell infiltration (Supporting Information Fig. 2). T-cell deficiency only had little or no effect on IC deposition (compare TCRβ/δ−/− with WT, Fig. 4C). Thus, Act1-deficiency results in variable disease symptoms in B6 and BALB/C mice, suggesting that epigenetic interactions within different strains play a role in disease specifications. Such phenomenon is well established and has previously been reported to differentially see more affect the susceptibility to autoimmunity [23]. After leaving the BM, immature T1 B cells travel to the spleen where they differentiate into T2 or T3 B cells in a B-cell receptor/BAFF-dependent manner [24], [25]. In BALB/C.Act1−/− and BAFF-Tg mice, B-cell hyperplasia and accelerated B-cell differentiation occur due to the cells’ heightened response to BAFF [2], and results in a skewing in the repertoire of transitional B cells toward the T2 B-cell phenotype (B220+AA4.1+CD23+IgM+), selleck inhibitor as well as increased levels of T3 and marginal zone (MZ) B cells [2, 25].

As T cells may represent a possible source of BAFF [26, 27], we evaluated if BAFF-driven T2/T3/MZ B-cell accumulation was present in TKO mice. Sixteen- to eighteen-week-old B6.Act1−/− mice expressed significantly increased numbers of total immature AA4.1+B220+ B cells (p < 0.05 as compared with WT mice, Fig. 5A). Levels of immature B cells were also increased in TCRβ/δ−/− mice and trended toward an increase in TKO mice (Fig. 5A). Mature B cells, including both MZ and FM B-cell subset, were significantly elevated in T-cell-deficient mice regardless of Act1 expression (Fig. 5A–B) as previously described by others [28], while classical PC (B220lowIgD−CD138+) were significantly reduced as a result of T-cell deficiency (Fig. 5C and Supporting Information Fig. 3A–C). B6.Act1−/− mice also displayed elevated levels of MZ B cells, but we found no increase in the number of FM B cells (Fig. 5B).

1a), and mice of this age were used for all subsequent

studies. Following seeding by the bone marrow lymphoid progenitors, T-cell commitment and development occurs in the DN thymocyte population (LMPP), which can be divided into subsets based on CD44 and CD25 expression, after excluding all lineage-positive cells. In the DN thymocyte population, the ETPs: Lin−, CD44+, CD25−, c-Kithi, IL-7Rα−/lo have been suggested to be the precursor for all thymocytes with T-lineage potential.[21] Unlike the significantly lower percentages of the proposed bone marrow-derived precursors (CLP, LMPP)[6] there was no significant difference in the ETP populations of Ts65Dn and euploid mice as a percentage of total thymocyte number, indicating that there was no preferential loss of ETP compared with other thymocyte populations Fulvestrant clinical trial (Fig. 1b). However, because of the thymic involution NVP-LDE225 chemical structure of the Ts65Dn mice, there were fewer ETPs in the thymus of Ts65Dn mice in comparison to euploid mice, although the differences were not significant (Fig. 1c). Further analysis of the DN subsets indicated that Ts65Dn mice had a lower percentage of DN1 (CD44+ CD25−), DN2 (CD44+ CD25+) and DN3 (CD44− CD25+) thymocytes compared with euploid mice (Fig. 1d). There was no significant difference in the percentage of DN4 thymocytes.

As a result of decreased thymic cellularity, Ts65Dn mice had approximately threefold to fourfold fewer total DN1, DN2 and DN3 thymocytes with no preferential loss of a single subset. C-X-C chemokine receptor type 7 (CXCR-7) The decreased number of DN4 thymocytes in the Ts65Dn mice was not significantly different (Fig. 1e). Similarly, there were significantly fewer mature thymocytes, with twofold decreases in the number of double-positive (DP) and CD4 single-positive (SP) thymocytes in Ts65Dn mice compared with euploid mice (see Supplementary material; Fig. S1a). However, there were not significant differences in percentage representation of the mature thymocyte populations in the Ts65Dn thymus in comparison to euploid mice (Fig. S1b) with the exception of an increased percentage of CD8 SP thymocytes. Hence, early thymocyte development during T-cell commitment

is altered in Ts65Dn mice but more mature thymocyte populations are relatively unaffected. To determine how the changes in the lymphoid progenitor cells in the bone marrow and thymus may affect mature lymphocyte homeostasis and function, the composition of the spleen was examined. In contrast to the thymus, there were no significant differences in splenic size and cellularity between Ts65Dn mice (10·9 ± 1·6 ×× 107 cells/spleen) and euploid mice (11·56 ± 1·56 × 107 cells/spleen; n = 10) or in the majority of the subsets. Similar to a previous report,[7] there was a slight increase in the percentage of TCR+ T cells, and a slight decrease in the percentage of CD19+ cells, but these changes were not significant (not shown).

After centrifugation

of the purified bacteria, 1 mL of the pellet [0.8 × 106 DNA copies of FAM cycle threshold (Ct) at 21.41] was used to infect fresh selleck inhibitor XTC-2, Vero or L929 cells (control) for 1 h at room temperature. Then, 4 mL of either fresh L-15M medium (5% FBS) or MEM (4% FBS) that was either supplemented with (2%) TPB or unsupplemented (growth control) was added to the culture flasks containing each cell line. All of the inoculated flasks were incubated at 28 °C. The medium was replaced every week with fresh medium (L-15M or MEM with or without TPB) for 3 weeks to ensure adequate nutrition. Finally, to verify that R. felis was successfully maintained in Vero and L929 cells, subpassages were performed every 3 weeks. Each experiment was performed at least twice. The viability and growth rate of R. felis in XTC-2, Vero and L929 cells were detected using quantitative PCR (qPCR), Gimenez staining and indirect fluorescent-antibody (IFA) staining of cytospin preparations. For qPCR, a specific probe (6FAM-AGGTGATGGAGAGGTTACCGGTGGAG-TAMRA) and a primer pair (Fwd: 5′-CCGTTGCCGGTAGCTTGTAT-3′; Rev: 5′-GCATTTGCAGCCCCCTCTAT-3′) were designed to target the cell surface antigen-like protein Sca7 gene of R. felis. Relative quantification of the qPCR results was performed as described by Mba et al. (2011). For IFA staining, a mouse monoclonal

Forskolin in vitro antibody against R. felis was used to confirm the intracellular growth of R. felis, which was monitored by Gimenez staining. Comparative analysis of R. felis replication was investigated in amphibian Ergoloid and mammalian cells inoculated with R. felis species in two culture media, L-15M and MEM, which were unsupplemented or supplemented with TPB. Using L-15M:TPB medium, qPCR, Gimenez and IFA results showed that R. felis replicated better in XTC-2 cells than in either mammalian cell line on day 7 (50 × 106 DNA copies), but both XTC-2 and L929 cells enabled better R. felis growth

(40–50 × 106 DNA copies) than did Vero cells (9 × 106 DNA copies) (Table 1, Supporting Information, Fig. S1) on day 14. A cytopathic effect of infected cells was observed for Vero and L929 cells during the third and second weeks, respectively, using inverted phase contrast microscopy (Fig. S2). When using MEM:TPB medium, qPCR showed that R. felis growth was similar in Vero and L929 cells after 7 days whereas at day 14, R. felis growth was greater in L929 cells (50 × 106 DNA copies) than in Vero cells (10 × 106 DNA copies) (Table 1). Overall, R. felis growth was similar in Vero and L929 cells in both MEM:TPB medium and L-15M:TPB medium at day 7, but R. felis grew better in L929 cells than in Vero cells at day 14 in both media and grew to similar levels in L929 cells and XTC-2 cells in L-15M:TPB medium (Table 1). Using media with and without TPB, we found a positive effect of TPB on R.

A short course of high-dose IL-2 starting on the day of BMT can up-regulate the SOCS-3 expression of donor naive CD4+ T cells. The proliferation and Th1-type polarization of donor naive CD4+ T cells inducibly expressing SOCS-3 is inhibited, which inhibits immunity to allogeneic antigen and aGVHD. Our animal experiment provided strong support for this hypothesis. Clearly, IL-2 pre-incubation can inhibit fully MHC-mismatched mice fatal aGVHD; but

donor lymphocytes incubated with IL-2 for 4 h injected immediately into recipients did not inhibit aGVHD. If the lymphocytes inducibly expressing SOCS-3 were stimulated with allogeneic antigen for 72 h, see more aGVHD could be inhibited significantly. A possible explanation is that it needs time for donor lymphocytes to receive the antigen presented by host APC, but SOCS-3 is a short-lived gene product induced in lymphocytes by IL-2. Pexidartinib mw SOCS-3 could not generate inhibition to aGVHD unless the lymphocytes inducibly expressing SOCS-3 receive allogeneic antigen

in time. Methods of inhibiting aGVHD, such as glucocorticosteroid, anti-thymocyte globulin, cyclosporin A and methylaminopterin, inhibit the whole immune system, and this can lead to the inhibition of graft-versus-tumour effects and serious infections. The aim of this study was to adjust the direction of polarization of Th and to inhibit excessive proliferation during aGVHD; the animal experimental results show the effectiveness of our aim. IL-2 pre-incubation can prevent aGVHD through up-regulating the expression

of SOCS-3 and inhibiting the proliferation of Th1-type polarization of naive CD4+ T cells. Inositol monophosphatase 1 Hopefully, these will provide new pathways for the inhibition of aGVHD. This paper was supported by the Great Biology and Medicine Foundation of Key Problems in Science and the Technology of Shanghai Science and Technology Committee (no. 06DZ19013). We acknowledge Dr Wan Yin (Department of immunology, Shanghai Medical College, Fudan University), who supported us very much during the initiation of our work. None. “
“Chronic granulomatous disease (CGD) is a primary immunodeficiency defined by mutations in the NADPH oxidase complex leading to reduced superoxide production, increased susceptibility to infection, chronic inflammation, and recurring abscess and granuloma formation. Here, we found that CGD mice were hyperresponsive to abscess-inducing T-cell-dependent carbohydrate antigens (glycoantigens) due to a ten-fold increase in NO production within APCs, which is known to be necessary for glycoantigen presentation on MHC class II. CGD mice exhibited increased Th1 pro-inflammatory T-cell responses in vitro and in vivo, characterized by more severe abscess pathology. This phenotype was also seen in WT animals following adoptive transfer of neutrophil-depleted APCs from CGD animals, demonstrating that this phenotype was independent of neutrophil and T-cell defects.

Results: Mpo−/− mice developed more severe nephritis than wildtype mice 20 and 40 weeks (23.1 ± 2.5 versus 40.2 ± 5.3 % abnormal glomeruli, P < 0.01) after pristane injection, despite having reduced glomerular deposition of IgG and complement. Enhancement of renal disease in MPO-deficient mice correlated

with increased accumulation of CD4 T cells, macrophages and neutrophils in glomeruli. This was, in turn, associated with augmented generation Target Selective Inhibitor Library of CD4 T cell responses (9.9 ± 1.7 versus 23.7 ± 1.3 % proliferating CD4 cells, P < 0.001) and increased activation and migration of dendritic cells in the spleen and lymph nodes. MPO deficiency also increased cellular apoptosis, leukocyte accumulation and pro-inflammatory cytokine expression in the peritoneum. Conclusions: MPO suppresses the development of pristane-induced lupus nephritis by inhibiting the early inflammatory response in the peritoneum and limiting the generation of CD4 T cell responses in secondary lymphoid organs. 154 L-CARNITINE SUPPLEMENTATION DURING GESTATION AND LACTATION IMPROVE GLUCOSE INTOLERANCE INDUCED BY MATERNAL SMOKING IN THE OFFSPRING I AL-ODAT1,2, H CHEN1, A SAWIRIS2, C POLLOCK2,

S SAAD2 1School of Medical and Molecular Biosciences, The University of Technology Sydney, Sydney, New South Wales; selleck chemicals llc 2Renal group/Kolling Institute of Medical research, Royal North Shore Hospital, St Leonards, New South Wales, Australia Aim: To investigate the role of maternal

L-carnitine supplement in antagonizing the deleterious effect of maternal SE on kidney development and glucose tolerance in female mice offspring. Background: Continuing maternal cigarette smoke exposure (SE) induces renal underdevelopment in the offspring at birth and glucose intolerance at adulthood. While L-carnitine has a beneficial role in embryogenesis in vitro, its role on kidney development and glucose tolerance in vivo is not known. Methods: Female Balb/c 4��8C breeder mice were exposed to either cigarette smoke or sham exposed for 6 weeks prior to mating, during gestation and lactation. A subgroup of the SE dams was treated with L-carnitine (SE+L-C) during gestation and lactation via drinking water. Female offspring were sacrificed at postnatal day (P) 1, P20 (weaning age) and 13 weeks (mature age). Kidneys were harvested and markers of renal development were determined. Intraperitoneal glucose tolerance test was performed at 12 weeks. Results: At P1, offspring from the SE+L-C group showed an increase in the body weight compared to those from non-treated dams (P < 0.05).