Effects of Lactobacillus on Interleukin-4 (IL-4), Tumour Necrosis Factor-Alpha (TNF-Alpha) and Immune Function in Allergic Rhinitis Rats

2022 ◽  
Vol 12 (1) ◽  
pp. 221-225
Author(s):  
Liang Jiang ◽  
Dianzhong Liu ◽  
Xiaoyan Hu
Keyword(s):  
Allergic Rhinitis ◽  
Critical Role ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Mucosal Inflammation ◽  
Model Group ◽  
Blank Group ◽  
Sd Rat ◽  
Experimental Group ◽  
Th1 And Th2

Allergic rhinitis (AR) is a type of nasal mucosal inflammation. Lactobacillus plays a critical role in maintaining micro-ecological balance. This study aims to detect its effects on IL-4, TNF-α, Th1 and Th2 in AR sprapue-dawley (SD) rat after lactobacillus intervention. Ovalbumin (OVA) allergic AR SD rat model was established and assigned into model group, experimental group and blank group followed by analysis of Nasal mucosa under the microscope, IL-4 and TNF-α level by ELISA and immunohistochemistry assay, and Th1 and Th2 cells in spleen by flow cytometry. AR symptom in experimental group was significantly severe compared to blank group, but relative better compared to model group (p < 0.05). Nasal mucosal hyperemia and inflammation was significantly ameliorated in experimental group with significantly increased Th1 cells and Th1/Th2 ratio and decreased Th2 cells compared to model group (p < 0.05). In conclusion, Lactobacillus intervention reduced IL-4 and TNF-α expression in serum and tissue and ameliorated the inflammation in AR rat.

scholarly journals Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production

1997 ◽  
Vol 186 (10) ◽  
pp. 1737-1747 ◽  
Author(s):  
Lauren Cohn ◽  
Robert J. Homer ◽  
Anthony Marinov ◽  
John Rankin ◽  
Kim Bottomly
Keyword(s):  
Airway Inflammation ◽  
Critical Role ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Direct Role ◽  
Mucus Production ◽  
Cell Recruitment ◽  
T Helper 2 ◽  
Asthmatic Patients ◽  
Th1 And Th2

Airway inflammation is believed to stimulate mucus production in asthmatic patients. Increased mucus secretion is an important clinical symptom and contributes to airway obstruction in asthma. Activated CD4 Th1 and Th2 cells have both been identified in airway biopsies of asthmatics but their role in mucus production is not clear. Using CD4 T cells from mice transgenic for the OVA-specific TCR, we studied the role of Th1 and Th2 cells in airway inflammation and mucus production. Airway inflammation induced by Th2 cells was comprised of eosinophils and lymphocytes; features found in asthmatic patients. Additionally, there was a marked increase in mucus production in mice that received Th2 cells and inhaled OVA, but not in mice that received Th1 cells. However, OVA-specific Th2 cells from IL-4–deficient mice were not recruited to the lung and did not induce mucus production. When this defect in homing was overcome by administration of TNF-α, IL-4 −/− Th2 cells induced mucus as effectively as IL-4 +/+ Th2 cells. These studies establish a role for Th2 cells in mucus production and dissect the effector functions of IL-4 in these processes. These data suggest that IL-4 is crucial for Th2 cell recruitment to the lung and for induction of inflammation, but has no direct role in mucus production.

scholarly journals Rapid Development of Th2 Activity During T Cell Priming

2003 ◽  
Vol 10 (1) ◽  
pp. 1-6 ◽  
Author(s):  
Adam F. Cunningham ◽  
Kai-Michael Toellner
Keyword(s):  
T Cells ◽  
T Cell ◽  
Rapid Development ◽  
Critical Role ◽  
Cell Polarization ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
Th 1 ◽  
Th1 And Th2

The paradigm of T helper-1 (Th-1) and Th-2 cells developing from non-committed naïve precursors is firmly established. Th1 cells are characterized by IFN production and, in mice, the selective switching to IgG2a. Conversely IL-4 production and selective switching to IgG1 and IgE characterize Th2 cells. Analysis of Th2 inductionin vitroindicates that this polarization develops gradually in T cells activated by anti-CD3 in the presence of IL-4; conversely anti-CD3 and IFN induce Th1 cells. In this report, we explore evidence that indicates that the T helper cell polarizationin vivocannot solely be explained by the cytokine environment. This is provided by studying the early acquisition of Th1 and Th2 activities during responses to a mixture of Th1 and Th2-inducing antigens. It is shown that these divergent forms of T cell help can rapidly develop in cells within a single lymph node. It is argued that early polarization to show Th-1 or Th-2 behavior can be induced by signals delivered during cognate interaction between virgin T cells and dendritic cells, in the absence of type 1 or type 2 cytokines. This contrasts with the critical role of the cytokines in reinforcing the Th-phenotype and selectively expanding T helper clones.

Stat6 Inhibits Human Interleukin-4 Promoter Activity in T Cells

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4529-4538 ◽  
Author(s):  
Steve N. Georas ◽  
John E. Cumberland ◽  
Thomas F. Burke ◽  
Rongbing Chen ◽  
Ulrike Schindler ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Regulatory Elements ◽  
Jurkat Cells ◽  
Proximal Promoter ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Th Cells

Abstract The differentiation of naive T-helper (Th) cells into cytokine-secreting effector Th cells requires exposure to multiple signals, including exogenous cytokines. Interleukin-4 (IL-4) plays a major role in this process by promoting the differentiation of IL-4–secreting Th2 cells. In Th2 cells, IL-4 gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple transcription factors to regulatory elements in the proximal promoter region. Nuclear factor of activated T cell (NFAT) family members play a critical role in regulating IL-4 transcription and interact with up to five sequences (termed P0 through P4) in the IL-4 promoter. The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known, although the IL-4–activated transcription factor signal transducer and activator of transcription 6 (Stat6) is required for this effect. We report here that Stat6 interacts with three binding sites in the human IL-4 promoter by electrophoretic mobility shift assays. These sites overlap the P1, P2, and P4 NFAT elements. To investigate the role of Stat6 in regulating IL-4 transcription, we used Stat6-deficient Jurkat T cells with different intact IL-4 promoter constructs in cotransfection assays. We show that, whereas a multimerized response element from the germline IgE promoter was highly induced by IL-4 in Stat6-expressing Jurkat cells, the intact human IL-4 promoter was repressed under similar conditions. We conclude that the function of Stat6 is highly dependent on promoter context and that this factor promotes IL-4 gene expression in an indirect manner.

scholarly journals Transforming growth factor β is dispensable for the molecular orchestration of Th17 cell differentiation

2009 ◽  
Vol 206 (11) ◽  
pp. 2407-2416 ◽  
Author(s):  
Jyoti Das ◽  
Guangwen Ren ◽  
Liying Zhang ◽  
Arthur I. Roberts ◽  
Xin Zhao ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Growth Factor ◽  
Th17 Cell ◽  
Th17 Cells ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Th2 Cells ◽  
Th17 Cell Differentiation ◽  
Th1 And Th2

Interleukin (IL)-17–producing T helper (Th17) cells play a critical role in the pathophysiology of several autoimmune disorders. The differentiation of Th17 cells requires the simultaneous presence of an unusual combination of cytokines: IL-6, a proinflammatory cytokine, and transforming growth factor (TGF) β, an antiinflammatory cytokine. However, the molecular mechanisms by which TGF-β exerts its effects on Th17 cell differentiation remain elusive. We report that TGF-β does not directly promote Th17 cell differentiation but instead acts indirectly by blocking expression of the transcription factors signal transducer and activator of transcription (STAT) 4 and GATA-3, thus preventing Th1 and Th2 cell differentiation. In contrast, TGF-β had no effect on the expression of retinoic acid receptor–related orphan nuclear receptor γt, a Th17-specific transcription factor. Interestingly, in Stat-6−/−T-bet−/− mice, which are unable to generate Th1 and Th2 cells, IL-6 alone was sufficient to induce robust differentiation of Th17 cells, whereas TGF-β had no effect, suggesting that TGF-β is dispensable for Th17 cell development. Consequently, BALB/c Stat-6−/−T-bet−/− mice, but not wild-type BALB/c mice, were highly susceptible to the development of experimental autoimmune encephalomyelitis, which could be blocked by anti–IL-17 antibodies but not by anti–TGF-β antibodies. Collectively, these data provide evidence that TGF-β is not directly required for the molecular orchestration of Th17 cell differentiation.

Peripheral Blood T-Helper Cells and Eosinophil Populations in Patients with Atopic and Nonatopic Chronic Rhinosinusitis

2017 ◽  
Vol 31 (1) ◽  
pp. e8-e12 ◽  
Author(s):  
Zhenxiao Huang ◽  
Jayakar V. Nayak ◽  
Yan Sun ◽  
Qian Huang ◽  
Bing Zhou
Keyword(s):  
Chronic Rhinosinusitis ◽  
Peripheral Blood ◽  
T Helper Cells ◽  
Nasal Polyps ◽  
Interferon Γ ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
T Helper ◽  
Helper Cells ◽  
Th1 And Th2

Background Analysis of recent research indicated that T-helper cells may play an important role in the pathogenesis of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) and CRS without nasal polyps (CRSsNP). Objective The purpose of this study was to investigate the peripheral blood Th1 and Th2 cells and eosinophil population in patients with CRS. Methods Peripheral blood samples were obtained from nine nonatopic controls, 37 patients with CRSsNP, and 66 patients with CRSwNP. The samples were then analyzed by flow cytometry analysis (Th1 cell [CD4+, interleukin 4−, interferon γ+]; and Th2 cell [CD4+, interleukin 4+, interferon γ−]). The patients were stratified into four groups based on their allergic status by using skin-prick test results and immunoglobulin E level measurements as the following: (1) nonatopic CRSsNP, (2) nonatopic CRSwNP, (3) atopic CRSsNP, and (4) atopic CRSwNP. Eosinophil counts were also compared. The severity of nasal diseases in these patients was assessed via the Lund-Mackay score. Results No significant differences in peripheral blood Th1 and Th2 cells were found among all the atopic, nonatopic CRS groups, and the nonatopic control groups. Peripheral blood eosinophil levels in atopic CRSwNP were significantly elevated compared with the nonatopic controls (p < 0.05), but no significant difference was found among all atopic and nonatopic CRS groups. Conclusion Analysis of our data demonstrated that a proportion of systemic Th1- and Th2-skewed lymphocytes in all CRS groups were similar to that in healthy subjects, irrespective of atopic status. The patients with CRSwNP and with atopy but not the patients with CRSsNP and with atopy demonstrated systemic eosinophilic inflammation. Further studies are needed to investigate underlying pathophysiologic mechanism or endotypes.

Stat6 Inhibits Human Interleukin-4 Promoter Activity in T Cells

Blood ◽  
1998 ◽  
Vol 92 (12) ◽  
pp. 4529-4538 ◽  
Author(s):  
Steve N. Georas ◽  
John E. Cumberland ◽  
Thomas F. Burke ◽  
Rongbing Chen ◽  
Ulrike Schindler ◽  
...  
Keyword(s):  
Gene Expression ◽  
T Cells ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Regulatory Elements ◽  
Jurkat Cells ◽  
Proximal Promoter ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Th Cells

The differentiation of naive T-helper (Th) cells into cytokine-secreting effector Th cells requires exposure to multiple signals, including exogenous cytokines. Interleukin-4 (IL-4) plays a major role in this process by promoting the differentiation of IL-4–secreting Th2 cells. In Th2 cells, IL-4 gene expression is tightly controlled at the level of transcription by the coordinated binding of multiple transcription factors to regulatory elements in the proximal promoter region. Nuclear factor of activated T cell (NFAT) family members play a critical role in regulating IL-4 transcription and interact with up to five sequences (termed P0 through P4) in the IL-4 promoter. The molecular mechanisms by which IL-4 induces expression of the IL-4 gene are not known, although the IL-4–activated transcription factor signal transducer and activator of transcription 6 (Stat6) is required for this effect. We report here that Stat6 interacts with three binding sites in the human IL-4 promoter by electrophoretic mobility shift assays. These sites overlap the P1, P2, and P4 NFAT elements. To investigate the role of Stat6 in regulating IL-4 transcription, we used Stat6-deficient Jurkat T cells with different intact IL-4 promoter constructs in cotransfection assays. We show that, whereas a multimerized response element from the germline IgE promoter was highly induced by IL-4 in Stat6-expressing Jurkat cells, the intact human IL-4 promoter was repressed under similar conditions. We conclude that the function of Stat6 is highly dependent on promoter context and that this factor promotes IL-4 gene expression in an indirect manner.

Clinical and Nasal Irrigation Fluid Findings in Perennial Allergic Rhinitis

1997 ◽  
Vol 11 (6) ◽  
pp. 435-442 ◽  
Author(s):  
Irakly Sulakvelidze ◽  
Mary Conway ◽  
Susan Evans ◽  
Paul I. Stetsko ◽  
Veljko Djuric ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Healthy Subjects ◽  
Inflammatory Marker ◽  
Interleukin 4 ◽  
Mucosal Inflammation ◽  
Prostaglandin E ◽  
Perennial Allergic Rhinitis ◽  
Irrigation Fluid ◽  
Nasal Irrigation ◽  
Nasal Steroid

Ten patients with perennial allergic rhinitis and 10 healthy subjects were studied to determine most discriminative nasal irrigation fluid marker(s) and to compare samples that were collected at baseline and over a 1-hour period, every 15 minutes. The latter were pooled and designated 1-hour sample. In the nasal irrigation we investigated the following inflammatory cells and soluble mediators: eosinophils, neutrophils, granulocyte-macrophage colony-stimulating factor, interleukin-4, interleukin-6, interleukin-8, ECP, EPX, MPO, leukotriene C4, leukotriene B4, prostaglandin E2, tryptase and fibrinogen. Patients with PAR were then treated for 2 weeks with the topical nasal steroid. The only marker that discriminated patients with perennial allergic rhinitis and healthy subjects was eosinophil count (EO%): correspondingly 14.01 ± 5.8 and 0.18 ± 0.09, (M ± SD). Difference between the studied groups did not depend on the time of irrigation, baseline or 1-hour. EO% was also the only marker of a clinically successful treatment with the nasal steroid, 14.01 ± 5.8 and 0.87 ± 0.4, before and after treatment respectively. We conclude that EO% is the most sensitive inflammatory marker of perennial allergic rhinitis, and that baseline nasal irrigation can be used to study nasal mucosal inflammation.

scholarly journals Mahuang Fuzi Xixin Decoction Attenuates Th1 and Th2 Responses in the Treatment of Ovalbumin-Induced Allergic Inflammation in a Rat Model of Allergic Rhinitis

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Mengyue Ren ◽  
Qingfa Tang ◽  
Feilong Chen ◽  
Xuefeng Xing ◽  
Yao Huang ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Rat Model ◽  
Immunoglobulin E ◽  
Allergic Inflammation ◽  
Wistar Rat ◽  
Serum Levels ◽  
Th2 Cells ◽  
Th2 Responses ◽  
Th1 And Th2 Responses ◽  
Th1 And Th2

Allergic rhinitis (AR) is one of the most common allergic diseases, which adversely affect patients’ quality of life. Mahuang Fuzi Xixin decoction (MFXD) has been widely used to treat AR in clinics in Asian countries. This study investigated the effect and possible therapeutic mechanisms of MFXD in the treatment of AR. A Wistar rat model of ovalbumin- (OVA-) induced AR was established and then treated with three doses of MFXD; AR symptoms, serum total immunoglobulin E, histamine, histopathological features, and release and expression of factors related to type 1 helper T (Th1) and type 2 helper T (Th2) responses were analyzed. Our study demonstrated that MFXD has a good therapeutic effect on OVA-induced allergic inflammation in an AR rat model as manifested in reduced frequencies of sneezing and nasal scratching and in reduced serum levels of total IgE and HIS. In addition, MFXD regulates imbalance in Th1/Th2 cells caused by AR by simultaneously attenuating Th1 and Th2 responses, such as by reducing the serum levels of IFN-γ and IL-4 and mRNA expression levels of IFN-γ, IL-4, GATA-3, and STAT-6. This study provided valuable information on the immunoregulatory effect of MFXD for the treatment of AR in future clinical studies.

Neutrophil Gelatinase-Associated Lipocalin From Macrophages Plays a Critical Role in Renal Fibrosis Via the CCL5 (Chemokine Ligand 5)-Th2 Cells-IL4 (Interleukin 4) Pathway

Hypertension ◽  
2021 ◽  
Author(s):  
Benjamin Bonnard ◽  
Jaime Ibarrola ◽  
Ixchel Lima-Posada ◽  
Amaya Fernández-Celis ◽  
Manon Durand ◽  
...  
Keyword(s):  
Renal Fibrosis ◽  
Critical Role ◽  
Collagen I ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Kidney Fibrosis ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Chemokine Ligand ◽  
Neutrophil Gelatinase

NGAL (neutrophil gelatinase-associated lipocalin; or lipocalin 2, Lcn2) is a novel mineralocorticoid target in the cardiovascular system. We showed that Lcn2 gene invalidation protects against proteinuria and renal injury upon mineralocorticoid excess and we hypothesized that NGAL produced from macrophages promotes the expression of chemoattractant molecules involved these renal lesions. The role of NGAL was analyzed using myeloid-specific (MΦ KO NGAL) Lcn2 knockout mice challenged with uni-nephrectomy, aldosterone, and salt (NAS) for 6 weeks. The role of the CCL5 (chemokine ligand 5) and IL4 (interleukin 4) in kidney fibrosis was studied by administration of the CCL5 receptor antagonist maraviroc or by injections of an anti-IL4 neutralizing antibody. In CTL mice, NAS increased the renal expression of extracellular matrix proteins, such as collagen I, αSMA, and fibronectin associated with interstitial fibrosis which were blunted in MΦ KO NGAL mice. The expression of CCL5 was blunted in sorted macrophages from MΦ KO NGAL mice challenged by NAS and in macrophages obtained from KO NGAL mice and challenged ex vivo with aldosterone and salt. The pharmacological blockade of the CCL5 receptor reduced renal fibrosis and the CD4 + Th cell infiltration induced by NAS. Neutralization of IL4 in NAS mice blunted kidney fibrosis and the overexpression of profibrotic proteins, such as collagen I, αSMA, and fibronectin. In conclusion, NGAL produced by macrophages plays a critical role in renal fibrosis and modulates the CCL5/IL4 pathway in mice exposed to mineralocorticoid excess.

scholarly journals Reversibility of T helper 1 and 2 populations is lost after long-term stimulation.

1996 ◽  
Vol 183 (3) ◽  
pp. 901-913 ◽  
Author(s):  
E Murphy ◽  
K Shibuya ◽  
N Hosken ◽  
P Openshaw ◽  
V Maino ◽  
...  
Keyword(s):  
Immune Response ◽  
Single Cells ◽  
Interleukin 4 ◽  
Th2 Cells ◽  
Th1 Cells ◽  
T Helper ◽  
T Helper 1 ◽  
Ifn Gamma ◽  
Th1 And Th2

Commitment of T helper 1 (Th1) or Th2 populations developing during an immune response to a pathogen, or an inappropriate immune response to an allergen or autoantigen, may determine the difference between health and chronic disease. We show that strongly polarized Th1 and Th2 populations assessed by immunoassay are heterogeneous using flow cytometry to detect single cells producing interferon gamma (IFN-gamma) and interleukin 4 (IL-4). Th1 populations arising after 1 wk of stimulation in IL-12 plus anti-IL-4 antibodies could convert to Th2 cells when restimulated in IL-4. Th2 populations resulting from stimulation for 1 wk in IL-4 could give rise to Th1 cells upon restimulation in IL-12 plus anti-IL-4. In contrast, the cytokine profiles of long-term Th1 and Th2 populations arising originally from repeated stimulation in IL-12 or IL-4 appeared more homogeneous and were not reversible, although IL-4 dramatically reduced the number of IFN-gamma-producing Th1 cells. This may explain previous reports that Th1 cells can be converted to Th2 cells.

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