scholarly journals IL-33 Enhanced the Proliferation and Constitutive Production of IL-13 and IL-5 by Fibrocytes

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Hisako Hayashi ◽  
Akiko Kawakita ◽  
Shintaro Okazaki ◽  
Hiroki Murai ◽  
Motoko Yasutomi ◽  
...  

Interleukin-33 appears to play important roles in the induction of allergic airway inflammation. However, whether IL-33 is involved in airway remodeling remains unclear. Because fibrocytes contribute to tissue remodeling in the setting of chronic inflammation, we examined the effects of IL-33 on fibrocyte functions. Fibrocytes were generatedin vitrofrom peripheral blood mononuclear cells by culturing in the presence of platelet derived growth factors and the cells were stimulated with IL-33. IL-33 enhanced cell proliferation,α-SMA expression, and pro-MMP-9 activity by the fibrocytes without increasing endogenous transforming growth factor-β1 production. Fibrocytes constitutively expressed IL-13 and IL-5, and their production was augmented by stimulation with IL-33. Dexamethasone inhibited the functions of fibrocytes, but IL-33 made fibrocytes slightly refractory to the inhibitory effect of dexamethasone in terms of IL-13 production. Montelukast suppressed IL-13 production by nonstimulated fibrocytes but not those stimulated by IL-33. These findings suggest that IL-33 is involved in the airway remodeling process through its modulation of fibrocyte function independent of antigen stimulation. IL-33 might partially reduce the therapeutic effects of glucocorticoid and cysteinyl leukotriene receptor antagonist on fibrocyte-mediated Th2 responses.

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Mahboubeh Baheri ◽  
Mohammadreza Dayer ◽  
Narges Baharifar ◽  
Abdolkarim Sheikhi ◽  
Abolfazl Sheikh

Background: Multiple Sclerosis (MS) is an autoimmune and inflammatory disorder of the central nervous system (CNS), which is associated with the imbalance of pro- and anti-inflammatory cytokines. Evidence indicates that nutritional interventions have some immunomodulatory impacts. Objectives: In this study, we investigated the effect of olive vegetation water (OVW) on IFN-γ and IL-10 secretion by peripheral blood mononuclear cells (PBMCs) of MS patients. Methods: In this study, PBMCs of MS patients were separated by Ficoll-Hypaque centrifugation. The cytotoxicity of OVW was assessed by the MTT assay. The treatments were performed for 48 and 72 hours, and IFN-γ and IL-10 were measured by ELISA. Results: No cytotoxicity was observed for OVW. Besides, OVW showed a significant inhibitory effect on IFN-γ secretion but augmenting effect on IL-10 secretion by PBMCs dose-dependently. Conclusions: This study indicated that OVW could have immunoregulatory effects on inflammatory reactions in MS patients.


2005 ◽  
Vol 79 (23) ◽  
pp. 14526-14535 ◽  
Author(s):  
Carlos F. Narváez ◽  
Juana Angel ◽  
Manuel A. Franco

ABSTRACT We have previously shown that very few rotavirus (RV)-specific T cells that secrete gamma interferon circulate in recently infected and seropositive adults and children. Here, we have studied the interaction of RV with myeloid immature (IDC) and mature dendritic cells (MDC) in vitro. RV did not induce cell death of IDC or MDC and induced maturation of between 12 and 48% of IDC. Nonetheless, RV did not inhibit the maturation of IDC or change the expression of maturation markers on MDC. After treatment with RV, few IDC expressed the nonstructural viral protein NSP4. In contrast, a discrete productive viral infection was shown in MDC of a subset of volunteers, and between 3 and 46% of these cells expressed NSP4. RV-treated IDC secreted interleukin 6 (IL-6) (but not IL-1β, IL-8, IL-10, IL-12, tumor necrosis factor alpha, or transforming growth factor beta), and MDC released IL-6 and small amounts of IL-10 and IL-12p70. The patterns of cytokines secreted by T cells stimulated by staphylococcal enterotoxin B presented by MDC infected with RV or uninfected were comparable. The frequencies and patterns of cytokines secreted by memory RV-specific T cells evidenced after stimulation of peripheral blood mononuclear cells (PBMC) with RV were similar to those evidenced after stimulation of PBMC with RV-infected MDC. Finally, IDC treated with RV strongly stimulated naive allogeneic CD4+ T cells to secrete Th1 cytokines. Thus, although RV does not seem to be a strong maturing stimulus for DC, it promotes their capacity to prime Th1 cells.


Pathogens ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 758 ◽  
Author(s):  
Ai-Ling Tian ◽  
Xiaowei Tian ◽  
Dan Chen ◽  
Mingmin Lu ◽  
Guillermo Calderón-Mantilla ◽  
...  

The liver fluke Fasciola gigantica has a remarkable ability to establish a long-term infection within the hepatobiliary system of the mammalian definitive host. F. gigantica achieves this by producing excretory–secretory molecules, which have immunomodulatory activities. In an effort to elucidate the immunomodulatory functions of F. gigantica thioredoxin peroxidase protein (FgTPx), we expressed recombinant FgTPx (rFgTPx) in Escherichia coli bacteria and examined its effects on several functions of goat peripheral blood mononuclear cells (PBMCs) in vitro. Sequence analysis revealed that FgTPx is related to a thioredoxin-like superfamily. Western blot analysis showed that rFgTPx was recognized by the sera of goats experimentally infected by F. gigantica. The specific binding of rFgTPx protein to the surface of goat PBMCs was demonstrated by immunofluorescence staining. We investigated the influence of serial concentrations of rFgTPx on various functions of goat PBMCs. All concentrations of rFgTPx increased the secretion of interleukin-2 (IL-2), IL-4, IL-10, IL-17, transforming growth factor-beta (TGF-β), and interferon gamma (IFN-γ), but inhibited PBMC proliferation, migration, and monocyte phagocytosis. Goat PBMCs exposed to 20–40 μg/mL of rFgTPx secreted increased levels of nitric oxide (NO), and 10–40 μg/mL of rFgTPx promoted cell apoptosis. These findings indicate that rFgTPx influences various functions of goat PBMCs by interacting with a large number of cellular targets, ultimately to promote the parasite’s survival. The roles of rFgTPx and their interacting proteins warrant further investigation.


Blood ◽  
2008 ◽  
Vol 111 (7) ◽  
pp. 3675-3683 ◽  
Author(s):  
Xingmin Feng ◽  
Sachiko Kajigaya ◽  
Elena E. Solomou ◽  
Keyvan Keyvanfar ◽  
Xiuli Xu ◽  
...  

Abstract Regulatory T cells (Treg) play important roles in suppressing immune responses and maintaining tolerance. Rabbit antithymocyte globulin (rATG) and horse ATG (hATG) are widely used in the treatment of immune-mediated syndromes, but their effects on Treg are unknown. We show here that in vitro culture of normal human peripheral blood mononuclear cells (PBMCs) with a low-dose rATG resulted in marked expansion of functional Treg by converting CD4+CD25− T cells to CD4+CD25+ T cells. hATG did not expand but rather decreased Treg. Immuno-blot showed increased expression of FOXP3 and NFAT1 in CD4+CD25− and CD4+CD25+ T cells exposed to rATG. PBMCs treated with rATG displayed increased interleukin-10 in culture supernatants than those treated with hATG. Furthermore, rATG and hATG showed differences in their potential to stimulate CD4+ T cells as examined using different activation markers. Microarray revealed that rATG induced markedly different gene-expression patterns in PBMCs, compared with hATG-treated or untreated PBMCs. Our findings indicate that rATG expanded Treg, probably through transcriptional regulation by enhanced NFAT1 expression, in turn conferring CD4+CD25− T cell FOXP3 expression and regulatory activity. The therapeutic effects of rATG may occur not only because of lymphocyte depletion but also enhanced Treg cell number and function.


2016 ◽  
Vol 310 (11) ◽  
pp. F1182-F1191 ◽  
Author(s):  
Ken Iseri ◽  
Masayuki Iyoda ◽  
Hirokazu Ohtaki ◽  
Kei Matsumoto ◽  
Yukihiro Wada ◽  
...  

Recent studies have demonstrated that conditioned media derived from mesenchymal stem cells (MSC-CM) have therapeutic effects in various experimental diseases. However, the therapeutic mechanism is not fully understood. In the present study, we investigated the therapeutic effects and mechanism of MSC-CM in experimental antiglomerular basement membrane glomerulonephritis. We administered either MSC-CM or vehicle from day 0 to day 10 after the induction of nephrotoxic serum nephritis in Wistar-Kyoto rats. In vitro, we analyzed the effects of MSC-CM on TNF-α-mediated cytokine production in cultured normal human mesangial cells, proximal tubular (HK-2) cells, human umbilical vein endothelial cells, and monocytes (THP-1 and peripheral blood mononuclear cells). Compared with vehicle treatment, MSC-CM treatment improved proteinuria and renal dysfunction. Histologically, MSC-CM-treated rats had reduced crescent formation and glomerular ED1+ macrophage infiltration and increased glomerular ED2+ macrophage infiltration. Increased serum monocyte chemoattractant protein (MCP)-1 levels were observed in MSC-CM-treated rats. Renal cortical mRNA expression levels of proinflammatory cytokines, such as TNF-α and IL-6, and of the T helper cell 1 cytokine interferon-γ were greatly decreased by MSC-CM treatment. In vitro, pretreatment with MSC-CM blocked TNF-α-mediated IL-8 release in normal human mesangial cells and HK-2 cells. TNF-α-mediated MCP-1 release was enhanced by pretreatment with MSC-CM in human umbilical vein endothelial cells and HK-2 cells and was strikingly enhanced in THP-1 cells. Stimulation of peripheral blood mononuclear cells with a combination of MCP-1 and IL-4 enhanced the expression of M2-associated genes compared with IL-4 alone. We demonstrated that MSC-CM had therapeutic effects in experimental antiglomerular basement membrane glomerulonephritis that were mediated through anti-inflammatory effects that were partly due to acceleration of M2 macrophage polarization, which might be mediated by MCP-1 enhancement.


Cells ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 78 ◽  
Author(s):  
Sarah Sasse ◽  
Anna Skorska ◽  
Cornelia Aquilina Lux ◽  
Gustav Steinhoff ◽  
Robert David ◽  
...  

Background: Bone marrow (BM)-derived stem cells with their various functions and characteristics have become a well-recognized source for the cell-based therapies. However, knowledge on their therapeutic potential and the shortage for a cross-link between distinct BM-derived stem cells, primed after the onset of myocardial infarction (MI), seems to be still rudimentary. Therefore, the post-examination of the therapeutic characteristics of such primed hematopoietic CD133+ and mesenchymal CD271+ stem cells was the object of the present study. Methods and Results: The effects of respective CD133+ and CD271+ mononuclear cells alone as well as in the co-culture model have been explored with focus on their angiogenic potential. The phenotypic analysis revealed a small percentage of isolated cells expressing both surface markers. Moreover, target stem cells isolated with our standardized immunomagnetic isolation procedure did not show any negative alterations following BM storage in regard to cell numbers and/or quality. In vitro network formation relied predominantly on CD271+ stem cells when compared with single CD133+ culture. Interestingly, CD133+ cells contributed in the tube formation, only if they were cultivated in combination with CD271+ cells. Additional to the in vitro examination, therapeutic effects of the primed stem cells were investigated 48 h post MI in a murine model. Hence, we have found a lower expression of transforming growth factor βeta 3 (TGFβ3) as well as an increase of the proangiogenic factors after CD133+ cell treatment in contrast to CD271+ cell treatment. On the other hand, the CD271+ cell therapy led to a lower expression of the inflammatory cytokines. Conclusion: The interactions between CD271+ and CD133+ subpopulations the extent to which the combination may enhance cardiac regeneration has still not been investigated so far. We expect that the multiple characteristics and various regenerative effects of CD271+ cells alone as well as in combination with CD133+ will result in an improved therapeutic impact on ischemic heart disease.


2019 ◽  
Vol 2019 ◽  
pp. 1-9
Author(s):  
Yu Long ◽  
Yuqing He ◽  
Fengming Jie ◽  
Sixin Li ◽  
Yanli Wu ◽  
...  

Object. To investigate the effect of Kuijieling (KJL) on the balance between T helper 17 (Th17) and regulatory T (Treg) cells in peripheral blood mononuclear cells (PBMC) in vitro and explore the underlying mechanism. Materials and Methods. PBMCs isolated from rats were stimulated with transforming growth factor-β, interleukin (IL)-6, and IL-23 to induce the imbalance of Th17 and Treg cells and were treated with 10, 5, or 2.5% KJL-containing serum. The proportion of Th17 or Treg cells in CD4+ T cells was analyzed by flow cytometry, the concentrations of IL-17, IL-21, and IL-10 were assayed by ELISA, mRNA expressions of retinoic acid-related orphan receptor γt (RORγt), forkhead box protein 3 (Foxp3), and signal transducer and activator of transcription 3 (STAT3) were quantified by PCR, and phosphorylated STAT3 (p-STAT3) was analyzed by flow cytometry. Results. KJL-containing serum decreased the proportion of Th17 cells and increased the proportion of Treg cells in CD4+ T cells, decreased the concentration of IL-17 and IL-21, enhanced the level of IL-10 in the cell culture supernatant, promoted the expression of Foxp3, and inhibited the levels of RORγt, STAT3, and p-STAT3. Conclusion. KJL suppresses the STAT3 pathway to remedy the imbalance between Th17 and Treg cells.


2021 ◽  
Author(s):  
Jiraporn Kantapan ◽  
Nampeung Anukul ◽  
Nipapan Leetrakool ◽  
Gwenaël Rolin ◽  
Jackie Vergote ◽  
...  

Abstract Background: Cells-based therapy is a highly promising treatment paradigm in ischemic disease due to its ability to repair tissues when implanted into a damaged site. These therapeutic effects have been involving a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. Therefore, the secreted therapeutic can be modulated by preconditioning the cells during in vitro culture. Herein, we investigated the potential use of magnetic resonance imaging (MRI) probes “Iron-Quercetin complex” or IronQ for preconditioning peripheral blood mononuclear cells (PBMCs) to expand proangiogenic cells and enhance their secreted therapeutic factors. Methods: PBMCs obtained from healthy donor blood were cultured in the presence of the Iron-Quercetin complex. Preconditioning-PBMCs differentiated cells were characterized by immunostaining. An enzyme-linked immunosorbent assay to describe the secreted cytokines. In vitro migration and tubular formation using human umbilical vein endothelial cells (HUVECs) were completed to investigate the proangiogenic efficacy.Results: IronQ significantly increased mononuclear progenitor cells' proliferation and differentiation into the spindle-shape-like cells, expressing both hematopoietic and stromal cell markers. The expansion increased the number of colony-forming units (CFU-Hill). The conditioned medium obtained from IronQ-treated PBMCs contained a high level of Interleukin (IL)-8, IL-10, urokinase-type-plasminogen-activator (uPA), matrix metalloproteinases-9 (MMP-9), and tumor necrosis factor-alpha (TNF-α), and augmented migration and capillary network formation of HUVEC and fibroblast cells in vitro.Conclusions: Our study demonstrated that the IronQ-precondition PBMCs protocol could enhance the angiogenic and reparative potential of non-mobilized PBMCs. This protocol can be used as an adjunctive strategy to improve cell therapy's efficacy of PBMCs for ischemic diseases and chronic wound.


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