Expression Of Related Cytokines Research Articles

VSL#3 probiotics exerts the anti-inflammatory activity via PI3k/Akt and NF-κB pathway in rat model of DSS-induced colitis

VSL#3 probiotics can be effective on induction and maintenance of the remission of clinical ulcerative colitis. However, the mechanisms are not fully understood. The aim of this study was to examine the effects of VSL#3 probiotics on dextran sulfate sodium (DSS)-induced colitis in rats. Acute colitis was induced by administration of DSS 3.5 % for 7 days in rats. Rats in two groups were treated with either 15 mg VSL#3 or placebo via gastric tube once daily after induction of colitis; rats in other two groups were treated with either the wortmannin (1 mg/kg) via intraperitoneal injection or the wortmannin + VSL#3 after induction of colitis. Anti-inflammatory activity was assessed by myeloperoxidase (MPO) activity. Expression of inflammatory related mediators (iNOS, COX-2, NF-κB, Akt, and p-Akt) and cytokines (TNF-α, IL-6, and IL-10) in colonic tissue were assessed. TNF-α, IL-6, and IL-10 serum levels were also measured. Our results demonstrated that VSL#3 and wortmannin have anti-inflammatory properties by the reduced disease activity index and MPO activity. In addition, administration of VSL#3 and wortmannin for 7 days resulted in a decrease of iNOS, COX-2, NF-κB, TNF-α, IL-6, and p-Akt and an increase of IL-10 expression in colonic tissue. At the same time, administration of VSL#3 and wortmannin resulted in a decrease of TNF-α and IL-6 and an increase of IL-10 serum levels. VSL#3 probiotics therapy exerts the anti-inflammatory activity in rat model of DSS-induced colitis by inhibiting PI3K/Akt and NF-κB pathway.

Expression profiles of Th17 pathway related genes in human systemic lupus erythematosus

Recently, evidence is emerging that inappropriate regulation of type 17 T helper cells (Th17) plays a fundamental role in the development of many autoimmune diseases including systemic lupus erythematosus (SLE). However, the role of Th17-related cytokines in SLE remains elusive. To further investigate the role and imbalance of Th17-related cytokines in the pathogenesis of SLE. A Quantitative RT-PCR Array (Human Th17 for Autoimmunity & Inflammation PCR Array) analyses were performed to study Th17-related genes expression in peripheral white blood cells of 25 new-onset patients with SLE and 15 healthy subjects. When gene expression for SLE patients was compared to the mean of normal controls, among the 84 target genes related to Th17 pathway, 7 (CXCL1, ICAM1, IL10, IL5, IL8, ISG20, JAK2,) were upregulated and 6 (CD28, CD40LG, S1PR1, IL17RE, IL23R, RORC) downregulated. However, comparisons of mRNA expression of Th17 related cytokines between lupus nephritis (LN) patients and SLE patients without nephritis (SLE non LN) showed no significant difference. In conclusion, SLE patients and normal controls showed different expression of a few genes in Th17 pathway, indicating that the pathway may be involved in the pathogenesis of SLE.

Expression of IL-22, IL-22R and IL-23 in the peri-implant soft tissues of patients with peri-implantitis

ObjectivesThe aim of this study was to compare the expression of interleukin (IL)-22, IL-22R and IL-23 in the peri-implant soft tissues between the peri-implantitis patient group (PG) and peri-implant healthy control group (HG). MethodsThe tissues were collected from 12 peri-implantitis patients and eight peri-implant healthy controls. Immunohistochemistry (IHC) and real-time quantitative PCR (qPCR) were performed to analyse the gene expression of IL-22, IL-22R and IL-23p19 in peri-implant soft tissues in the PG and the HG group. ResultsThe IHC result showed that number of IL-22, IL-22R, and IL-23p19 positive cells increased in PG than in HG (P<0.05). The result of qPCR demonstrated that the expressions of IL-22 messenger RNA (mRNA) and IL-23p19 mRNA were significantly higher in the PG group compared to the HG group (P<0.05). Gene expression of IL-22R mRNA was higher in the PG group; however, there was no statistically significant difference between these two groups (P>0.05). ConclusionsThis study indicates that there is an increased expression level of IL-22 and IL-23 in patients with peri-implantitis, which may induce expression of related pro-inflammatory cytokines and may further have a crucial role in tissue repair and reconstruction in pathogenesis of peri-implantitis.

Treatment with Ligands for Toll-Like Receptors 2 and 5 Induces a Mixed T-helper 1- and 2-Like Response in Chicken Splenocytes

Toll-like receptors (TLRs) play an important role in the induction of host responses to pathogens. Interactions between TLRs and their ligands result in the production of cytokines that modulate the adaptive immune response through polarizing CD4+ T cells into either T-helper (T(H))1 or T(H)2 phenotypes. In this regard, TLR2 and TLR5 ligands have been shown to induce responses in mammals that are biased toward T(H)1 or T(H)2 phenotypes. However, whether a similar phenomenon occurs in chickens remains to be elucidated. To this end, chicken splenocytes were stimulated with the TLR2 ligand Pam3CSK4 and the TLR5 ligand flagellin, and the relative expression of several cytokines and transcription factors was quantified at 1, 3, 8, and 18 h poststimulation. The results suggest that both TLR ligands induce a mixed T(H)1- and T(H)2-like response, as characterized by the upregulation of both the T(H)1-associated cytokine interferon-γ and the T(H)1-inducing cytokine interleukin (IL)-12, in addition to the T(H)2-associated cytokine IL-4, and in the case of flagellin, IL-13 as well. Future studies may be aimed at assessing the adjuvant potential of these ligands.

Immunomodulatory effect of polysaccharides from submerged cultured Cordyceps gunnii

Context: The genus Cordyceps (Clavicipitaceae) is a group of entomopathogenic fungi that is widely used as tonic food or invigorant with broad-spectrum medicinal properties in China. Cordyceps gunnii (Berk.)Berk (C. gunnii), is also well known as the Chinese rare caterpillar fungus and has similar pharmacological activities with Cordyceps sinensis (C. sinensis). Polysaccharides (PS) from various Cordyceps species have demonstrated many interesting biological activities, including antitumor, immunopotentiation, hypoglycemic, and hypocholesterolemic activities.Objective: To investigate the effect of C. gunnii PS on the immunostimulatory antitumor function and expression of immune related cytokines in normal, immuno-suppressive, and H22-bearing mice, respectively. Methods: C. gunnii PS were extracted with hot water at 80°C for 2 h. Normal, immuno-suppressive, and H22-bearing mice were treated with PS respectively. By detecting the value of macrophage phagocytic index, proliferation of lymphocytes, natural killer (NK) cell activity and expression of related cytokines, interleukin (IL-4), tumor necrosis factor-α (TNF-a) and interferon-γ (IFN-γ), and tumor inhibition index in H22-bearing mice additionally, the effect of PS on immunostimulatory antitumor function and its mechanism were studied.Results: The total sugar content of the PS was determined to be 95% after purification. PS markedly increased the thymus and spleen indexes, the macrophage phagocytosis, the proliferation of splenic cells, and the level of IFN-γ and TNF-α. In tumor growth inhibition test, PS showed remarkable inhibition effects.Conclusion: PS from the C. gunnii could enhance nonspecific immunological function, humoral immunity, cellular immunity in mice, and inhibit tumor growth.

Decreased RNA expression of interleukin 17A in skin of leprosy

Interleukin-17A (IL-17A) is a proinflamatory cytokine that plays an important role in fighting pathogens at mucosal interfaces, by summoning neutrophils and upregulating cytoplasmatic antimicrobial peptides. So far, the presence of IL-17A in leprosy has not been demonstrated. The expression of IL-17A and related cytokines (IL-6 and IL-23p19) was addressed through RNA extraction and cDNA quantitative amplification in macerated biopsies of active lesions of 48leprosy patients and 20fragments of normal skin of individuals. Blood levels of IL-17A, IL-23p19 and IL-6 were determined by ELISA. We found an abrogated mRNA IL-17A response in all biopsies of leprosy patients, as compared with controls. Circulating IL-17A and IL-23p19 were undetectable in both patients and controls, but IL-6 was higher in lepromatous patients. Although at low levels, IL-17A mRNA in lepromatous patients had an inverse linear correlation with bacillary burden. Low expression of IL-17A in patients may be a constitutive genetic feature of leprosy patients or a circumstantial event induced by the local presence of the pathogen, as an escape mechanism.

Immunomodulatory Effects of Bone Marrow-Derived Mesenchymal Stem Cells in a Swine Hemi-Facial Allotransplantation Model

BackgroundIn this study, we investigated whether the infusion of bone marrow-derived mesenchymal stem cells (MSCs), combined with transient immunosuppressant treatment, could suppress allograft rejection and modulate T-cell regulation in a swine orthotopic hemi-facial composite tissue allotransplantation (CTA) model.Methodology/Principal FindingsOutbred miniature swine underwent hemi-facial allotransplantation (day 0). Group-I (n = 5) consisted of untreated control animals. Group-II (n = 3) animals received MSCs alone (given on days −1, +1, +3, +7, +14, and +21). Group-III (n = 3) animals received CsA (days 0 to +28). Group-IV (n = 5) animals received CsA (days 0 to +28) and MSCs (days −1, +1, +3, +7, +14, and +21). The transplanted face tissue was observed daily for signs of rejection. Biopsies of donor tissues and recipient blood sample were obtained at specified predetermined times (per 2 weeks post-transplant) or at the time of clinically evident rejection. Our results indicated that the MSC-CsA group had significantly prolonged allograft survival compared to the other groups (P<0.001). Histological examination of the MSC-CsA group displayed the lowest degree of rejection in alloskin and lymphoid gland tissues. TNF-α expression in circulating blood revealed significant suppression in the MSC and MSC-CsA treatment groups, as compared to that in controls. IHC staining showed CD45 and IL-6 expression were significantly decreased in MSC-CsA treatment groups compared to controls. The number of CD4+/CD25+ regulatory T-cells and IL-10 expressions in the circulating blood significantly increased in the MSC-CsA group compared to the other groups. IHC staining of alloskin tissue biopsies revealed a significant increase in the numbers of foxp3+T-cells and TGF-β1 positive cells in the MSC-CsA group compared to the other groups.ConclusionsThese results demonstrate that MSCs significantly prolong hemifacial CTA survival. Our data indicate the MSCs did not only suppress inflammation and acute rejection of CTA, but also modulate T-cell regulation and related cytokines expression.

Prolonged allergen challenge in a guinea pig model of allergic rhinitis leads to nasal mucosa remodeling

The aim of this study was to use a guinea pig model of prolonged allergic-induced rhinitis to characterize the feature of nasal mucosa remodeling. Forty-eight male Hartley guinea pigs were randomly divided into six groups: allergen challenged groups (Group OVA(2w) , Group OVA(6w) and Group OVA(12w)) and control groups respectively (Group Sal(2w), Group Sal(6w) and Group Sal(12w)). Each group had 8 guinea pigs. To develop a guinea pig model of nasal mucosa remodeling, ovalbumin-sensitized guinea pigs were repeatedly challenged with allergen twice a week from two weeks to 12 weeks. Matched control groups were challenged with physiological saline. Nasal lavage was performed 24 hours after the last intranasal challenge. Then nasal mucosa were obtained. HE, AB-PAS, MT, and immunohistochemical staining against transforming growth factor-beta1 (TGF-beta1) were performed. Eosinophil cationic protein (ECP) and OVA-special IgE (OVA-sIgE) were detected by ELISA in nasal lavage fluid. (1) The levels of OVA-sIgE in nasal lavage fluid in Group OVA(6w) and Group OVA(12w) were significantly different from Group OVA(2w), while the levels of ECP had no significant difference among the experiment groups. The levels of OVA-sIgE and ECP in experiment groups were significantly different from control groups respectively (P < 0.01). (2) Grade 0 and Grade 1 of epithelial damage were significantly different in Group OVA(6w) and Group OVA(12w) when compared with from Group OVA(2w) (P < 0.01). At the same time, Grade 0 and Grade 1 of epithelial damage were statistically different in the experiment groups when compared with the respectively control groups (P < 0.05). (3) Goblet gland hyperplasia and collagen deposit within the extracellular matrix (ECM) were easily found in Group OVA(6w) and Group OVA(12w) compared with Group OVA(2w) (P < 0.01). The number of goblet gland and the ratio of collagen deposit were statistically more in Group OVA(6w) and Group OVA(12w) than in Group Sal(6w) and Group Sal(12w) (P < 0.05). That feature of the ratio of collagen deposit did not show in Group OVA(2w) versus Group Sal(2w). (4) Increased TGF-beta1 expressions were observed in Group OVA(6w) and Group OVA(12w) compared with Group OVA(2w) (P < 0.01). Those increasing expressions were also observed in experiment groups rather than in the respectively control groups (P < 0.01). Epithelial damage, goblet cells hyperplasia and collagen deposition in ECM were observed as the features of remodeling in this guinea pig model of allergic rhinitis under prolonged allergen challenge. Epithelial damage, excessive expression of related cytokines and enhancement activity of enzymes were observed in early time after challenge of allergen. The features of goblet cells hyperplasia and collagen deposition in ECM were observed at a later stage.

The Effects of Selenium Source on Measures of Selenium Status of Mares and Selenium Status and Immune Function of Their Foals

The effect of organic and inorganic sources of selenium (Se) on measures of Se status of mares and their foals, Se concentrations of colostrum and milk, and indices of immune function of foals was studied. Twenty late-gestation Standardbred mares were randomly assigned to one of two groups. All mares received an identical balanced ration, except for the source of supplementary Se: one group received organic Se (Se yeast) and the other group received inorganic Se (sodium selenite), fed to deliver 0.3 mg/kg supplementary Se based on total ration dry matter. Mares received the experimental diet from 2 months before estimated due date until 1 month after foaling. Source of Se did not affect Se concentrations in maternal plasma, red blood cells, colostrum, or milk. At 1 month of age, foals from mares fed organic Se had higher red blood cell Se concentration than foals from mares fed inorganic Se (P < .05). Measures of immunity included serum immunoglobulin G concentration, lymphocyte proliferation in response to concanavalin A, and relative cytokine gene expression of stimulated lymphocytes (interferon gamma [IFNγ], interleukin [IL]-2, IL-5, IL-10, tumor necrosis factor alpha [TNFα]) and neutrophils (IL-1, IL-6, IL-8, IL-12, TNFα). Relative gene expression of IL-2, TNFα, and IFNγ by foal lymphocytes was associated with the source of Se supplementation provided to the mares. We conclude that the source of dietary Se provided to mares may influence the immune function of foals at 1 month of age through changes in relative gene expression of certain lymphocyte cytokines.

Imbalance of regulatory T cells to Th17 cells in IgA nephropathy

Background. Dysregulation of CD4 + T cell subsets participates in the pathogenesis of IgA nephropathy (IgAN). FoxP3 + regulatory T cells (Treg) and Th17 cells are two novel subsets of CD4 + T cells. This study aims to investigate Treg/Th17 balance in IgAN patients. Methods. Peripheral frequencies of Th17 and Treg functional subsets – CD45RA + FoxP3low resting Treg (rTreg) and CD45RA-FoxP3high activated Treg (aTreg) were assessed in 63 adult IgAN patients. Expression of transcription factors (FoxP3 and RORγt) and related cytokines of Treg and Th17 were analysed. Renal expression of FoxP3 and IL-17A were detected by immunohistochemistry. Results. Compared with normal controls, IgAN patients had decreased frequency of CD45RA-FoxP3high aTreg subset (p < 0.05), increased frequency of Th17 (p < 0.05) and decreased ratio of Treg/Th17 (p < 0.05). Frequency of aTreg subset correlated with SBP(r = − 0.57, p < 0.05), DBP (r = − 0.50, p < 0.05), eGFR (r = 0.68, p < 0.05) and 24 h proteinuria (r = − 0.58, p < 0.05). RORγtmRNA/FoxP3mRNA ratio increased in IgAN (p < 0.05). Serum IL-17A, IL-21, IL-23, IL-1β and IL-6 elevated while IL-10 decreased in IgAN (p < 0.05), and serum IL-17A correlated with 24 h proteinuria (r = 0.35, p < 0.05). Serum TGF-β1 wasn't different between the two groups. Renal interstitial infiltration of FoxP3 + mononuclear cells were observed in IgAN patients, particularly prominent in those with > 25% tubular atrophy/interstitial fibrosis. Tubular IL-17A expression was found in 34 out of 63 IgAN patients. Compared with 29 patients without IL-17A expression, these patients had lower renal function, greater proteinuria, and more severe tubulointerstitial damage. Conclusions. Imbalance of Treg/Th17 found in IgAN may play a role in disease pathogenesis and progression.

Prolonged matrix metalloproteinase-3 high expression after cyclic compressive load on human synovial cells in three-dimensional cultured tissue

Excessive mechanical stress is thought to be a factor in the development of joint disorders through the expression of matrix metalloproteinases (MMPs) and related cytokines. Although studies revealed that mechanical stress on the synovium induces MMP expression, it is still not known which MMPs prolonged high level expression. The authors focused on MMP-3, which is one of the major factors in joint disorders such as rheumatism and temporomandibular joint disorders. They examined mRNA and protein levels of MMP-3, other MMPs and related cytokines after loading stress. Human synovial cells were seeded onto a collagen scaffold and different magnitudes of cyclic compressive load were applied for 1h. Time-dependent mRNA and protein levels for catabolic genes were examined after loading. mRNA expressions of MMP-1, MMP-3, MMP-9, IL-6, IL-8 and IL-1β increased after excessive compression. In particular, only mRNA of MMP-3 was up-regulated and maintained at a high level for 24h after excessive loading. The concentrations of MMP-3, IL-6 and IL-8 in culture media after loading increased with excessive compression. These results may account for the pathomechanism of MMP-3 induced by cyclic load on synovial cells in joint disorders.

Azuki bean (Vigna angularis) extract inhibits the development of experimentally induced atopic dermatitis-like skin lesions in NC/Nga mice

The present study investigated the effects of azuki bean (Vigna angularis) extract (VAE) on the progress of atopic dermatitis (AD)-like skin lesions in NC/Nga mice induced by 1-chloro-2,4-dinitrobenzene. The efficacy of VAE in NC/Nga mice was determined by measuring gross and histological skin lesions, serum IgE levels, eosinophil ratio in peripheral leucocytes, and mRNA expression levels of interleukin (IL)-4, tumour necrosis factor (TNF)-α and interferon (IFN)-γ in splenocytes. Continuous ingestion of VAE inhibited the development of the AD-like skin lesions in a dose-dependent manner. In the VAE-treated mice, the numbers of mast cells in the skin, eosinophil ratio in peripheral leucocytes, relative mRNA expression of inflammatory cytokines in the spleen, and serum IgE levels were significantly reduced. Results suggest that VAE can inhibit the development of AD-like skin lesions in NC/Nga mice by regulating immune mediators and cells, and may be an effective alternative therapy for AD.

Endothelial Cells Derived From Human iPSCS Increase Capillary Density and Improve Perfusion in a Mouse Model of Peripheral Arterial Disease

Stem cell therapy for angiogenesis and vascular regeneration has been investigated using adult or embryonic stem cells. In the present study, we investigated the potential of endothelial cells (ECs) derived from human induced pluripotent stem cells (hiPSCs) to promote the perfusion of ischemic tissue in a murine model of peripheral arterial disease. Endothelial differentiation was initiated by culturing hiPSCs for 14 days in differentiation media supplemented with BMP-4 and vascular endothelial growth factor. The hiPSC-ECs exhibited endothelial characteristics by forming capillary-like structures in matrigel and incorporating acetylated-LDL. They stained positively for EC markers such as KDR, CD31, CD144, and eNOS. In vitro exposure of hiPSC-ECs to hypoxia resulted in increased expression of various angiogenic related cytokines and growth factors. hiPSC-ECs were stably transduced with a double fusion construct encoded by the ubiquitin promoter, firefly luciferase for bioluminescence imaging and green fluorescence protein for fluorescent detection. The hiPSC-ECs (5×10(5)) were delivered by intramuscular injection into the ischemic hindlimb of SCID mice at day 0 and again on day 7 after femoral artery ligation (n=8). Bioluminescence imaging showed that hiPSC-ECs survived in the ischemic limb for at least 2 weeks. In addition, laser Doppler imaging showed that the ratio of blood perfusion was increased by hiPSC-EC treatment by comparison to the saline-treated group (0.58±0.12 versus 0.44±0.04; P=0.005). The total number of capillaries in the ischemic limb of mice receiving hiPSC-EC injections was greater than those in the saline-treated group (1284±155 versus 797±206 capillaries/mm(2)) (P<0.002). This study is a first step toward development of a regenerative strategy for peripheral arterial disease based on the use of ECs derived from hiPSCs.

Cellular immune responses, chemokine, and cytokine profiles in turkey poults following infection with the intestinal parasite Eimeria adenoeides

Cellular immune responses, chemokine, and cytokine profiles were investigated in 20-d-old turkey poults following an oral infection with 12.5 × 10(3) oocysts of Eimeria adenoeides, a protozoan parasite of the genus Eimeria that develops in the ceca. Large numbers of oocysts were produced in the feces of infected birds from d 5 after infection followed by a rapid decline by d 7. Local immune activities were characterized by observing the extent of leukocyte infiltration in the ceca by histology, measuring subsets of the lymphocyte population by immunohistochemistry, and determining the relative expression of cytokines by real-time, reverse-transcription PCR. Inflammation, assessed by scoring the extent of cellular infiltration of leukocytes in sections of ceca, was significantly higher in infected poults compared with uninfected poults on d 4, 7, 9, and 11 following infection. The percent area occupied by CD4+ and CD8+ cells in the ceca was significantly greater on d 9 and 11 (CD4+) and d 11 (CD8+) in infected poults compared with uninfected controls. The relative expression of the chemokine CXCLi2 and the cytokines interleukin (IL) 1β, interferon (IFN) γ, IL13, and IL10 was investigated in tissue samples taken from the ceca. Increased expression of CXCLi2 occurred on d 4 and 7. Increased expression of IL10 and IFNγ occurred on d 4 and of IL1β and IL13 occurred on d 7 postinfection. The increased leukocyte infiltration in the ceca, alterations in the lymphocyte subpopulations, and changes in expression of chemokines and cytokines are an indication of the cell-mediated immune mechanisms occurring in the host as a result of exposure to E. adenoeides.

Anti-inflammatory and immunomodulatory efficacy of indigenous probiotic Lactobacillus plantarum Lp91 in colitis mouse model

Probiotics can affect the immune homeostasis by altering the gut microbial balance and enhancing the immune system of gut, thus benefits in Inflammatory Bowel Disease, including Crohn's disease and Ulcerative colitis. Relative gene expression of pro, anti-inflammatory cytokines and other molecules in 2,4,6-trinitrobenzene sulfonic acid-induced colitis mouse model against Lactobacillus plantarum Lp91 (L. plantarum Lp91) was investigated by reverse transcription-quantitative PCR (RT-qPCR) using relative expression software tool (REST 2008 V2.0.7). L. plantarum Lp91 evoked significant down regulation of TNF-α and COX2 to 0.026 and 0.077 fold in colitis mouse model. No significant difference in expression of IL-12a cytokine in colitis mouse challenged with L. plantarum Lp91 was also observed. IL-10 was significantly up-regulated to 37.813 and 1.327 fold in colitis and non-colitis mouse challenged with L. plantarum Lp91. While, other anti-inflammatory markers i.e. COX1, IL-4 and IL-6 were significantly up regulated in colitis mouse challenged with L. plantarum Lp91. MUC2 gene was significantly up regulated to 2.216 fold in non-colitis group. L. plantarum Lp91, an indigenous probiotic culture, the main subject of this project exhibited strong immunemodulatory properties under in vivo conditions in mouse colitis model.

Influence of dietary ingredients on in vitro inflammatory response of intestinal porcine epithelial cells challenged by an enterotoxigenic Escherichia coli (K88)

Enterotoxigenic Escherichia coli (ETEC) K88 is the main bacterial cause of diarrhea in piglets around weaning and the adhesion of ETEC to the intestinal mucosa is a prerequisite step for its colonization. In this study, the adhesion of a fimbriated ETEC and a non-fimbriated E. coli (NFEC) to the intestinal cells and the activation of the innate immune system were evaluated using a porcine intestinal epithelial cell line (IPEC-J2). The impact of several feedstuffs (wheat bran (WB); casein glycomacropeptide (CGMP); mannan-oligosaccharides (MOS); locust bean extract (LB) and Aspergillus oryzae fermentation extract (AO)) on ETEC attachment and the inflammatory response were also studied. The gene expression of TLR-4; TLR-5; IL-1β; IL-8; IL-10 and TNF-α were quantified using Cyclophilin-A, as a reference gene, and related to a non-challenged treatment. The fimbriated strain was markedly better than the non-fimbriated strain at adherence to intestinal cells and inducing an inflammatory response. All the feedstuffs studied were able to reduce the adhesion of ETEC, with the greatest decrease with CGMP or MOS at highest concentration. Regarding the inflammatory response, the highest dose of WB promoted the lowest relative expression of cytokines and chemokines. All tested feedstuffs were able to reduce the adhesion of ETEC to IPEC-J2 and interfere on the innate inflammatory response; however WB should be further studied according to the beneficial results on the intestinal inflammatory process evidenced in this study.

Snapshot of spatio-temporal cytokine responses to single and co-infections with helminths and bacteria

Cytokines play a key role in maintaining communication between organs and in so doing modulate the interaction between concurrent infections. The extent of these effects depends on the properties of the organ infected and the intensity and type of infections. To determine systemic bystander effects among organs, IFN-γ, IL-4 and IL-10 gene expression was quantified at 7 days post-challenge in directly infected and uninfected organs during single and co-infections with the respiratory bacterium Bordetella bronchiseptica and the gastrointestinal helminths Graphidium strigosum and Trichostrongylus retortaeformis. Results showed that cytokine expression in a specific organ was influenced by the type of infection occurring in another organ, and this bystander effect was more apparent in some organs than others. Within the same organ the relative cytokine expression was consistent across infections, although some cytokines were more affected by bystander effects than others. For the infected gastrointestinal tract, a stronger cytokine response was observed in the tissue that harbored the majority of helminths (i.e. duodenum and fundus). Overall, co-infections altered the intensity but to a lesser extent the relative cytokine profile against the focal infection, indicating clear bystander effects and low organ compartmentalization. However, organs appear to actively modulate cytokine expression to avoid potential immuno-pathological consequences.

T Cell Factor-1 Negatively Regulates Expression of IL-17 Family of Cytokines and Protects Mice from Experimental Autoimmune Encephalomyelitis

Activated CD4 T cells are associated with protective immunity and autoimmunity. The manner in which the inflammatory potential of T cells and resultant autoimmunity is restrained is poorly understood. In this article, we demonstrate that T cell factor-1 (TCF1) negatively regulates the expression of IL-17 and related cytokines in activated CD4 T cells. We show that TCF1 does not affect cytokine signals and expression of transcription factors that have been shown to regulate Th17 differentiation. Instead, TCF1 regulates IL-17 expression, in part, by binding to the regulatory regions of the Il17 gene. Moreover, TCF1-deficient Th17 CD4 T cells express higher levels of IL-7Rα, which potentially promotes their survival and expansion in vivo. Accordingly, TCF1-deficient mice are hyperresponsive to experimental autoimmune encephalomyelitis. Thus, TCF1, a constitutively expressed T cell-specific transcription factor, is a critical negative regulator of the inflammatory potential of TCR-activated T cells and autoimmunity.

Expressions of estrogen receptor-α and related cytokines and their clinical correlation in patients with systemic lupus erythematosus (SLE)

Objective To study the mechanism of effects of estrogen receptor (ER) on T and B lymphocytes in patients with SLE and synergistic effect of T and B lymphocytes in the pathogenesis of SLE.Methods Real-time fluorescence quantitative PCR was performed to detect the mRNA expressions of ER-α,interleukin 10 (IL-10) and B lymphocyte stimulator (BLyS) in peripheral blood mononuclear cells (PBMCs)from 40 SLE patients and 40 normal human controls. The clinical and laboratory correlation with the levels of these parameters was analyzed. Results A significant increase was observed in the relative expression levels of ER-α, IL-10 and BLyS mRNA in SLE patients compared with the normal human controls (P ＜ 0.05 or 0.01 ), in active SLE patients compared with inactive SLE patients (P ＜ 0.05 or 0.01 ). Additionally, the mRNA expression levels of the 3 parameters were significantly correlated with the presence of renal damage, proteinuria, arthritis, etc. No statistical difference was observed in the mRNA expression levels of these parameters between female and male patients or between female and male normal controls. Conclusions IL-10 and BLyS appear to be correlated with the disease activity and severity of SLE, and ER-α may play an important role in the action mechanism of T and B lymphocytes in SLE.

Effects of curcumin in intestinal fibrosis of rats and its mechanism

Objective To investigate the anti-fibrotic effects of curcumin in trinitrobenzene sulphonic acid (TNBS) induced intestinal fibrosis in rats and its mechanism. Methods Forty SD rats were randomly divided into model group, treatment group, control group and normal group with 10each. Except the normal group, the other three groups were given 10, 15, 20, 25 and 30 mg of TNBS enema on the 1st, 8 th, 15th, 22nd and 29th days,respectively. The rats in treatment group were intraperitonealy injected with 30 mg/kg of curcumin daily. Control group was injected with 0. 9%NaCl solution and normal group received an equal volume of 50% ethanol enema without any treatment. The damage and fibrosis of colon were detected with HE staining and Masson collagen staining, respectively. The contents of interleukin (IL) -2, tumor necrosis factor (TNF) -α, IL-4 and IL-17 in colon were measured by enzyme-link immunosorbent analysis (ELISA). The expressions of intestinal fibrosis related cytokines such as transforming growth factor (TGF) -β1, connective tissue growth factor (CTGF), Smad3, collagen Ⅰ and collagen Ⅲ mRNA were determined by FQ-PCR.Results The macroscopic and micrpscopic colonic damage scores and collagen area were significantly higher in model group (6.14 ± 1.07, 8. 42 ± 1.40 and 36. 59% ± 4.07%, respectively) and control group (6.17 ± 1.47, 8. 17 ±1.47 and 37.18 %±4.05 %, respectively) than those in normal group (2.13±0.64, 2.25±1.28 and 25.43%±5.39% ,respectively)(P＜0.05). Contents of IL2, TNF-α, IL-17, as well as expressions of intestinal fibrosis related cytokines including TGF-β1, CTGF,Smad3, collagen Ⅰ and Ⅲ mRNA were also higher in model group [(378. 25±29. 90) ng/L,(87.11±23.85) ng/L, (47.80±5.62) ng/L, 4.71%±2.71%,10.33%±6.99%,9.35%±7.32%,1.52% ± 1.11% and 3.04% ±1.33%, respectively] and control group [(410. 06 ± 64.74) ng/L,(100.41±12.59) ng/L, (41.45±2. 12) ng/L, 4. 12%±3.01%,11.46%±4.72%,10. 11%±3.80%,1. 57% ± 1. 35% and 3. 03% ± 3. 53%, respectively] in comparision with normal group [(179.74±20. 73) ng/L, (35. 47±7. 13) ng/L, (14. 48±7. 52) ng/L and 0. 90%± 1. 13%,0.53%±0.47%, 0. 62%±0. 44%, 0. 16%±0. 09% and 0. 18%±0. 10%, respectively] (P＜0.05). While in treatment group, the macroscopic (4.00 ± 1.07 ) and micrpscopic (5. 13 ± 1.46)colonic damage scores, collagen area (30.01%±7.56%), contents of IL-2 [(223.91±28.04) ng/L],TNF-α [(44.19±4. 77) ng/L] and IL-17 [(14.89±4. 31) ng/L], expressions of TGF-β1 (0.85%±0.76%), CTGF (1.56%±1.13%), Smad3 (3.62%±3.03%), collagen Ⅰ (0.40%±0.31%) and Ⅲ (0.60 % ± 1.02 % ) mRNA were much lower than those in model group and control group (P＜0.05 ), but similar to those in normal group (P＞ 0.05 ). Conclusions Curcumin can inhibit intestinal fibrosis caused by excessive wound-healing reaction via reducing the overexpression of cytokines in colonic mucosa and attenuating the inflammation of colon. Key words: Curcumin; Colon; Fibrosis; Interleukin-2 ; Transforming growth factor beta 1; Smad3 protein; Rats,Sprague-Dawley