scholarly journals Anti-asthmatic effect of Ping-Chuan Formula in asthmatic mice, and its molecular mechanism of action

2021 ◽  
Vol 20 (11) ◽  
pp. 2325-2331
Author(s):  
Xi Ming ◽  
Wanchao Xu ◽  
Yazun Liu ◽  
Xinguang Zhang ◽  
Li Bai ◽  
...  
Keyword(s):  
Lung Tissue ◽  
Transforming Growth Factor ◽  
Promising Candidate ◽  
T Box ◽  
Mhc Ii ◽  
Forkhead Box ◽  
Candidate Drug ◽  
Ox40 Ligand ◽  
Molecular Mechanism Of Action ◽  
Ifn Γ

Purpose: To investigate the anti-asthmatic effect of Ping-Chuan Formula (PCF) in a mouse model, and the associated molecular mechanisms.Methods: Asthma mice were induced using ovalbumin (OVA), and PCF (600 mg/kg) was administered to the mice for 4 weeks. Sections of lung tissues were examined microscopically. The expressions of interleukins (ILs), interferon (IFN)-γ, transforming growth factor (TGF)-β were assayed, while lung tissue expressions of Toll like receptor (TLR)-4, GATA binding protein (GATA)-3, Ox40 ligand (OX40L), indoleamine 2,3-dioxygenase (IDO), and forkhead box P3 (Foxp3) determined. The T box expressed in T cells (T-bet) was evaluated using western blotting. The expressions of MHC II and co-stimulators (CD 11c, CD 80 and CD 86) of dendritic cells (DCs) were determined by flow cytometry.Results: PCF decreased inflammation in lung, and also down-regulated IL-4, -6, -17 and TGF-β (p < 0.01), whereas IL-10 and IFN-γ expressions were up-regulated (p < 0.01). Moreover, PCF decreased the expressions of TLR-4, GATA-3 and OX40L in lung tissue, and promoted Foxp3, IDO and T-bet. Besides, PCF decreased the levels of MHC II and co-stimulators (CD 80 and CD 86) on the surface of DCs.Conclusion: PCF exerts anti-asthmatic effect in mice via inhibition of inflammation, and modulation of MHC II and co-stimulators on the surface of DCs. These findings suggest that PCF is a promising candidate drug for treating asthma in humans.

scholarly journals Indoor PM2.5 from coal combustion aggravates ovalbumin-induced asthma-like airway inflammation in BALB/c mice

2019 ◽  
Vol 317 (1) ◽  
pp. L29-L38 ◽  
Author(s):  
Jie Yu ◽  
Kebin Li ◽  
Jie Xu
Keyword(s):  
Airway Inflammation ◽  
Lung Tissue ◽  
Coal Combustion ◽  
Transforming Growth Factor ◽  
Inflammatory Cells ◽  
Lavage Fluid ◽  
Control Group ◽  
Foxp3 Mrna ◽  
Neutrophil Sequestration ◽  
Ifn Γ

We hypothesized that indoor PM2.5 exposure from coal combustion exaggerates airway inflammation in the lung tissue of asthmatic mice induced with ovalbumin (OVA). Forty BALB/c mice, randomly divided into four groups ( n = 10 per group), were intratracheally instilled with normal saline alone, PM2.5 (2.5 mg/ml PM2.5 alone), OVA (15 μg/ml OVA alone), and PM2.5+OVA (2.5 mg/ml PM2.5 and 15 μg/ml OVA), respectively, four times at 2-wk intervals. Daily mean concentration of PM2.5 from indoor coal combustion was 156.95 μg/m3. The highest metal composition in PM2.5 was Zn (34.81 ± 1.8 μg/m3). Exposure to PM2.5+OVA significantly elevated IL-4 and decreased IFN-γ production in mice compared with the control ( P < 0.05). Exposure to PM2.5+OVA showed a significant increase in the protein levels of granulocyte-macrophage colony-stimulating factor and IL-8 and a decrease in the protein level of transforming growth factor-β1 in bronchoalveolar lavage fluid of mice compared with the control ( P < 0.05). The expression of IL-4 mRNA was significantly increased, whereas the expression of IFN-γ mRNA was decreased in lung tissue of the PM2.5+OVA group ( P < 0.05). The expression level of Foxp3 mRNA in the PM2.5+OVA group was significantly lower than that in the control group in lung tissue ( P < 0.05). Treatment with PM2.5+OVA promoted a prominent neutrophil sequestration into the lung parenchyma, goblet cell proliferation, and severe inflammatory cell infiltration in the airways. Exposure to PM2.5 from indoor coal combustion might induce airway inflammatory immune responses and exacerbate peribronchiolar inflammation due to infiltration of inflammatory cells into the airway submucosa and airway structural pathological changes.

Involvement of NF-κB in changes of IFN-γ-induced CIITA/MHC-II and iNOS expression by influenza virus in macrophages

2011 ◽  
Vol 48 (9-10) ◽  
pp. 1253-1262 ◽  
Author(s):  
Do Thi Thu Hang ◽  
Jae-Young Song ◽  
Min-Young Kim ◽  
Jin-Woo Park ◽  
Yeun-Kyung Shin
Keyword(s):  
Influenza Virus ◽  
Inos Expression ◽  
Mhc Ii ◽  
Ifn Γ

scholarly journals Intestinal Intraepithelial Lymphocytes Sustain the Epithelial Barrier Function against Eimeria vermiformis Infection

2006 ◽  
Vol 74 (9) ◽  
pp. 5292-5301 ◽  
Author(s):  
Kyoko Inagaki-Ohara ◽  
Fitriya Nurannisa Dewi ◽  
Hajime Hisaeda ◽  
Adrian L. Smith ◽  
Fumiko Jimi ◽  
...  
Keyword(s):  
Transforming Growth Factor ◽  
Cell Monolayer ◽  
Direct Interaction ◽  
Intraepithelial Lymphocytes ◽  
Epithelial Barrier ◽  
Necrosis Factor Alpha ◽  
Intestinal Intraepithelial Lymphocytes ◽  
Tnf Α ◽  
Ifn Γ ◽  
Eimeria Vermiformis

ABSTRACT Eimeria spp. are intracellular protozoa that infect intestinal epithelia of most vertebrates, causing coccidiosis. Intestinal intraepithelial lymphocytes (IEL) that reside at the basolateral site of epithelial cells (EC) have immunoregulatory and immunoprotective roles against Eimeria spp. infection. However, it remains unknown how IEL are involved in the regulation of epithelial barrier during Eimeria sp. infection. Here, we demonstrated two distinct roles of IEL against infection with Eimeria vermiformis, a murine pathogen: production of cytokines to induce protective immunity and expression of junctional molecules to preserve epithelial barrier. The number of IEL markedly increased when oocyst production reached a peak. During infection, IEL increased production of gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) and decreased transforming growth factor β (TGF-β) production. Addition of IFN-γ and TNF-α or supernatants obtained from cultured IEL from E. vermiformis-infected mice reduced transepithelial electrical resistance (TER) in a confluent CMT93 cell monolayer, a murine intestine-derived epithelial line, but antibodies against these cytokines suppressed the decline of TER. Moreover, TGF-β attenuated the damage of epithelial monolayer and changes in TER caused by IFN-γ and TNF-α. The expression of junctional molecules by EC was decreased when IEL produced a high level of IFN-γ and TNF-α and a low level of TGF-β in E. vermiformis-infected mice. Interestingly, IEL constantly expressed junctional molecules and a coculture of EC with IEL increased TER. These results suggest that IEL play important multifunctional roles not only in protection of the epithelium against E. vermiformis-induced change by cytokine production but also in direct interaction with the epithelial barrier when intra-EC junctions are down-regulated.

scholarly journals Role of Vitamin D in Premature Atherosclerosis in Adolescents Type 1 Diabetes through Transforming Growth Factor-β1, Interferon-γ, Interleukin-10, and Interleukin-17

2020 ◽  
Vol 8 (B) ◽  
pp. 738-746
Author(s):  
Haryudi Aji Cahyono ◽  
Wisnu Barlianto ◽  
Dian Handayani ◽  
Handono Kalim
Keyword(s):  
Vitamin D ◽  
Type 1 Diabetes ◽  
Transforming Growth Factor ◽  
Interleukin 10 ◽  
Interferon Γ ◽  
Transforming Growth Factor Β1 ◽  
Premature Atherosclerosis ◽  
Ifn Γ ◽  
Tgf Β1

BACKGROUND: Cardiovascular disease (CVD) is one the cause of mortality in patients with type 1 diabetes (T1D). The development of CVD is mainly triggered by atherosclerosis, which is associated with the inflammatory process. AIM: The current study was aimed to investigate the association of Vitamin D level and premature atherosclerosis in adolescents with T1D, mainly through the regulation of various cytokines (interferon-γ [IFN-γ], IL-17, interleukin-10 [IL-10], and transforming growth factor-β1 [TGF-β1]). METHODS: This study was designed as a cross-sectional study involving 40 T1D and 40 healthy control who came to the outpatient clinic, Saiful Anwar Hospital, Malang, Indonesia, within the study period (January 2019-July 2019). RESULTS: Our data demonstrated that the IFN-γ and IL-17 levels were significantly higher (p < 0.001), whereas the TGF-β1 and IL-10 levels were significantly lower (p < 0.001) in T1D group compared with control. Furthermore, T1D also has higher carotid intima-media thickness (cIMT) value and lower flow-mediated dilatation (FMD) value compared to the control group (p < 0.001). Level of 25(OH)D3 was strongly associated with reduced cIMT and elevated FMD (p < 0.005). The direct effect of 25(OH)D3 on cIMT and FMD was higher than the indirect effect of Vitamin D through TGF-β1, IL-10, IL-17, and IFN-γ. The cutoff value of 25(OH)D3 levels for the risk of atherosclerosis was 12.8 ng/dL (sensitivity 85.7% and specificity 86.7%). CONCLUSION: The level of Vitamin D in the T1D group was significantly lower than those in healthy children and Vitamin D deficiency substantially influences the formation of premature atherosclerosis.

scholarly journals Effects of Gamma Interferon, Interleukin-10, and Transforming Growth Factor β on the Survival of Mycobacterium avium subsp. paratuberculosis in Monocyte-Derived Macrophages from Naturally Infected Cattle

2004 ◽  
Vol 72 (4) ◽  
pp. 1974-1982 ◽  
Author(s):  
M. S. Khalifeh ◽  
J. R. Stabel
Keyword(s):  
Growth Factor ◽  
Cell Cultures ◽  
Mycobacterium Avium ◽  
Transforming Growth Factor ◽  
Transforming Growth Factor Β ◽  
Interleukin 10 ◽  
Gamma Interferon ◽  
Ifn Γ ◽  
Culture Supernatants

ABSTRACT Gamma interferon (IFN-γ) plays a significant role in the control of mycobacterial infections, including Mycobacterium avium subsp. paratuberculosis. However, the contribution of other immunoregulatory cytokines, such as interleukin-10 (IL-10) and transforming growth factor β (TGF-β), in Johne's disease has not been investigated as yet. In this study, we examined the effects of in vivo and in vitro infection with M. avium subsp. paratuberculosis on the production of IFN-γ, IL-10, and TGF-β by peripheral blood mononuclear cells (PBMC). We also examined the effects of exogenous IFN-γ, IL-10, and TGF-β on M. avium subsp. paratuberculosis survival in the cell cultures. PBMC obtained from naturally infected cows, regardless of their disease status, specifically upregulated IL-10 and TGF-β in culture supernatants in response to stimulation with live M. avium subsp. paratuberculosis. Nonstimulated PBMC recovered from subclinically infected animals secreted the lowest levels of TGF-β, but after stimulation with live M. avium subsp. paratuberculosis, TGF-β levels in the culture supernatants increased to levels similar to that produced by PBMC from healthy animals. The numbers of viable M. avium subsp. paratuberculosis recovered from cultures from naturally infected animals were higher than those from healthy cows after in vitro infection with M. avium subsp. paratuberculosis. The addition of exogenous IL-10 and TGF-β to PBMC isolated from healthy cows inhibited the bactericidal activity of these cells as evidenced by the increased number of viable M. avium subsp. paratuberculosis recovered from these cultures compared to cell cultures containing medium alone. These data suggest important immune regulatory roles for IL-10 and TGF-β during infection with M. avium subsp. paratuberculosis that may be directly related to their effects on macrophage activation and killing of M. avium subsp. paratuberculosis.

scholarly journals Generation of Human CD8 T Regulatory Cells by CD40 Ligand–activated Plasmacytoid Dendritic Cells

2002 ◽  
Vol 195 (6) ◽  
pp. 695-704 ◽  
Author(s):  
Michel Gilliet ◽  
Yong-Jun Liu
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cd8 T Cells ◽  
Transforming Growth Factor ◽  
Cd8 T Cell ◽  
Cd40 Ligand ◽  
Plasmacytoid Dendritic Cells ◽  
Target Cells ◽  
Ifn Γ

Although CD8 T cell–mediated immunosuppression has been a well-known phenomenon during the last three decades, the nature of primary CD8 T suppressor cells and the mechanism underlying their generation remain enigmatic. We demonstrated that naive CD8 T cells primed with allogeneic CD40 ligand–activated plasmacytoid dendritic cells (DC)2 differentiated into CD8 T cells that displayed poor secondary proliferative and cytolytic responses. By contrast, naive CD8 T cells primed with allogeneic CD40 ligand–activated monocyte-derived DCs (DC1) differentiated into CD8 T cells, which proliferated to secondary stimulation and killed allogeneic target cells. Unlike DC1-primed CD8 T cells that produced large amounts of interferon (IFN)-γ upon restimulation, DC2-primed CD8 T cells produced significant amounts of interleukin (IL)-10, low IFN-γ, and no IL-4, IL-5, nor transforming growth factor (TGF)-β. The addition of anti–IL-10–neutralizing monoclonal antibodies during DC2 and CD8 T cell coculture, completely blocked the generation of IL-10–producing anergic CD8 T cells. IL-10–producing CD8 T cells strongly inhibit the allospecific proliferation of naive CD8 T cells to monocytes, and mature and immature DCs. This inhibition was mediated by IL-10, but not by TGF-β. IL-10–producing CD8 T cells could inhibit the bystander proliferation of naive CD8 T cells, provided that they were restimulated nearby to produce IL-10. IL-10–producing CD8 T cells could not inhibit the proliferation of DC1-preactivated effector T cells. This study demonstrates that IL-10–producing CD8 T cells are regulatory T cells, which provides a cellular basis for the phenomenon of CD8 T cell–mediated immunosuppression and suggests a role for plasmacytoid DC2 in immunological tolerance.

scholarly journals Co-methylation analysis in lung tissue identifies pathways for fetal origins of COPD

2020 ◽  
Vol 56 (4) ◽  
pp. 1902347
Author(s):  
Priyadarshini Kachroo ◽  
Jarrett D. Morrow ◽  
Alvin T. Kho ◽  
Carrie A. Vyhlidal ◽  
Edwin K. Silverman ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Lung Function ◽  
Lung Tissue ◽  
Gestational Age ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Fetal Lung ◽  
Developmental Origins ◽  
Fetal Origins ◽  
Adult Lung

COPD likely has developmental origins; however, the underlying molecular mechanisms are not fully identified. Investigation of lung tissue-specific epigenetic modifications such as DNA methylation using network approaches might facilitate insights linking in utero smoke (IUS) exposure and risk for COPD in adulthood.We performed genome-wide methylation profiling for adult lung DNA from 160 surgical samples and 78 fetal lung DNA samples isolated from discarded tissue at 8–18 weeks of gestation. Co-methylation networks were constructed to identify preserved modules that shared methylation patterns in fetal and adult lung tissues and associations with fetal IUS exposure, gestational age and COPD.Weighted correlation networks highlighted preserved and co-methylated modules for both fetal and adult lung data associated with fetal IUS exposure, COPD and lower adult lung function. These modules were significantly enriched for genes involved in embryonic organ development and specific inflammation-related pathways, including Hippo, phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), Wnt, mitogen-activated protein kinase and transforming growth factor-β signalling. Gestational age-associated modules were remarkably preserved for COPD and lung function, and were also annotated to genes enriched for the Wnt and PI3K/AKT pathways.Epigenetic network perturbations in fetal lung tissue exposed to IUS and of early lung development recapitulated in adult lung tissue from ex-smokers with COPD. Overlapping fetal and adult lung tissue network modules highlighted putative disease pathways supportive of exposure-related and age-associated developmental origins of COPD.

scholarly journals Treatment of Experimental (Trinitrobenzene Sulfonic Acid) Colitis by Intranasal Administration of Transforming Growth Factor (Tgf)-β1 Plasmid

2000 ◽  
Vol 192 (1) ◽  
pp. 41-52 ◽  
Author(s):  
Atsushi Kitani ◽  
Ivan J. Fuss ◽  
Kazuhiko Nakamura ◽  
Owen M. Schwartz ◽  
Takashi Usui ◽  
...  
Keyword(s):  
Growth Factor ◽  
Sulfonic Acid ◽  
Transforming Growth Factor ◽  
Intraperitoneal Administration ◽  
Experimental Colitis ◽  
Inhibitory Effect ◽  
Transforming Growth Factor Β1 ◽  
Trinitrobenzene Sulfonic Acid ◽  
Ifn Γ ◽  
Tgf Β1

In this study, we show that a single intranasal dose of a plasmid encoding active transforming growth factor β1 (pCMV-TGF-β1) prevents the development of T helper cell type 1 (Th1)-mediated experimental colitis induced by the haptenating reagent, 2,4,6-trinitrobenzene sulfonic acid (TNBS). In addition, such plasmid administration abrogates TNBS colitis after it has been established, whereas, in contrast, intraperitoneal administration of rTGF-β1 protein does not have this effect. Intranasal pCMV-TGF-β1 administration leads to the expression of TGF-β1 mRNA in the intestinal lamina propria and spleen for 2 wk, as well as the appearance of TGF-β1–producing T cells and macrophages in these tissues, and is not associated with the appearances of fibrosis. These cells cause marked suppression of interleukin (IL)-12 and interferon (IFN)-γ production and enhancement of IL-10 production; in addition, they inhibit IL-12 receptor β2 (IL-12Rβ2) chain expression. Coadministration of anti–IL-10 at the time of pCMV-TGF-β1 administration prevents the enhancement of IL-10 production and reverses the suppression of IL-12 but not IFN-γ secretion. However, anti–IL-10 leads to increased tumor necrosis factor α production, especially in established colitis. Taken together, these studies show that TGF-β1 inhibition of a Th1-mediated colitis is due to: (a) suppression of IL-12 secretion by IL-10 induction and (b) inhibition of IL-12 signaling via downregulation of IL-12Rβ2 chain expression. In addition, TGF-β1 may also have an inhibitory effect on IFN-γ transcription.

scholarly journals Distinctive role of Stat3 and Erk-1/2 activation in mediating interferon-γ inhibition of TGF-β1 action

2006 ◽  
Vol 290 (5) ◽  
pp. F1234-F1240 ◽  
Author(s):  
Myrto Giannopoulou ◽  
Steven C. Iszkula ◽  
Chunsun Dai ◽  
Xiaoyue Tan ◽  
Junwei Yang ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Ectopic Expression ◽  
Interferon Γ ◽  
Signal Pathways ◽  
Tubular Epithelial Cells ◽  
Plasminogen Activator Inhibitor 1 ◽  
Ifn Γ ◽  
Pai 1

Interferon-γ (IFN-γ) is a multifunctional cytokine that elicits antifibrotic activity in a variety of organs. In this study, we investigated the potential role and mechanism of IFN-γ in modulating the fibrogenic action of transforming growth factor (TGF)-β1 in tubular epithelial cells. Incubation of human proximal tubular epithelial (HKC) cells with IFN-γ inhibited TGF-β1-mediated α-smooth muscle actin (α-SMA) expression. IFN-γ also abolished TGF-β1-induced fibronectin and plasminogen activator inhibitor-1 (PAI-1) expression. To explore the mechanisms by which INF-γ inhibits TGF-β1 action, the signaling pathways that are critical for mediating the antifibrotic activity of IFN-γ were studied. Stimulation of HKC cells with IFN-γ triggered a sustained activation of Erk-1/2 and signal transducer and activator of transcription-3 (Stat3). Blockade of Erk-1/2 activation with an Mek1 inhibitor abolished the inhibitory effect of IFN-γ on α-SMA expression, whereas inhibition of Stat3 activation had no influence. Constitutive activation of Erk-1/2 by ectopic expression of activated Mek1 mimicked IFN-γ and suppressed TGF-β1-mediated α-SMA expression. Interestingly, inhibition of Stat3 activation abolished the ability of IFN-γ to attenuate TGF-β1-mediated PAI-1 and fibronectin expression in HKC cells. These findings indicate that IFN-γ is capable of antagonizing the fibrogenic actions of TGF-β1 in renal tubular epithelial cells. The antifibrotic action of IFN-γ appears to be mediated through a coordinated activation of both Erk-1/2 and Stat3 signal pathways in a mutually independent fashion.

scholarly journals Predominance of Th1 Immune Response in Pleural Effusion of Patients with Tuberculosis among Other Exudative Etiologies

2019 ◽  
Vol 58 (1) ◽  
Author(s):  
Vinícius da Cunha Lisboa ◽  
Marcelo Ribeiro-Alves ◽  
Raquel da Silva Corrêa ◽  
Isabelle Ramos Lopes ◽  
Thiago Thomaz Mafort ◽  
...  
Keyword(s):  
Immune Response ◽  
Pleural Effusion ◽  
Transforming Growth Factor ◽  
Interleukin 2 ◽  
Principal Component ◽  
Transforming Growth Factor Β1 ◽  
Enzyme Linked Immunosorbent Assay ◽  
Biochemical Tests ◽  
Cross Sectional ◽  
Ifn Γ

ABSTRACT Pleural tuberculosis (PlTB), a common form of extrapulmonary TB, remains a challenge in the diagnosis among many causes of pleural effusion. We recently reported that the combinatorial analysis of interferon gamma (IFN-γ), IFN-γ-inducible protein 10 (IP-10), and adenosine deaminase (ADA) from the pleural microenvironment was useful to distinguish pleural effusion caused by TB (microbiologically confirmed or not) among other etiologies. In this cross-sectional cohort study, a set of inflammatory mediators was quantified in blood and pleural fluid (PF) from exudative pleural effusion cases, including PlTB (n = 27) and non-PlTB (nTB) (n = 25) patients. The levels of interleukin-2 (IL-2), IL-4, IL-6, IL-10, IL-17A, IFN-γ, tumor necrosis factor (TNF), IP-10, transforming growth factor β1 (TGF-β), and ADA were determined using cytometric bead assay, enzyme-linked immunosorbent assay (ELISA), or biochemical tests. IFN-γ, IP-10, TNF, TGF-β, and ADA quantified in PF showed significantly higher concentrations in PlTB patients than in nTB patients. When blood and PF were compared, significantly higher concentrations of IL-6 and IL-10 in PF were identified in both groups. TGF-β, solely, showed significantly increased levels in PF and blood from PlTB patients when both clinical specimens were compared to those from nTB patients. Principal-component analysis (PCA) revealed a T helper type 1 (Th1) pattern attributed mainly to higher levels of IP-10, IFN-γ, TGF-β, and TNF in the pleural cavity, which was distinct between PlTB and nTB. In conclusion, our findings showed a predominantly cellular immune response in PF from TB cases, rather than other causes of exudative effusion commonly considered in the differential diagnosis of PlTB.

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