scholarly journals Mechanical Growth Factor Promotes FOXP3 Expression in Regulatory T Cells and Enhances its Function in Treating Ankylosing Spondylitis

Author(s):  
Hongyu Qin ◽  
Shuangshuang Yuan ◽  
Hao Zeng ◽  
Hao Li ◽  
Jinsong Yang

Abstract BackgroundTo verify that mechanical growth factor (MGF) may be an effective target for treating ankylosing spondylitis. MethodsFOXP3 expression was measured in Treg cells from healthy male subjects treated with MGF. A rat model of ankylosing spondylitis was established, and the levels of ankylosing spondylitis-related factors (tumor necrosis factor [TNF]-α, interleukin [IL]-2, and IL-10) were measured. ResultsWe found that the proliferation and total number of Treg cells, as well as FOXP3 expression levels, increased significantly in the MGF-treated groups versus in the control. The levels of inflammation, bone destruction, and new bone formation were significantly decreased in animals treated with MGF compared to in the control group. TNF-α expression decreased significantly, while IL-2 and IL-10 levels increased significantly in the MGF group compared to in the control. ConclusionsMGF may delay disease progression in ankylosing rats by inducing FOXP3 expression, promote FOXP3+ Treg cell proliferation and differentiation and reducing the expression of TNF-α and increasing the expression of IL-10 and IL-2.

2021 ◽  
Author(s):  
Hongyu Qin ◽  
Shuangshuang Yuan ◽  
Hao Zeng ◽  
Hao Li ◽  
Jinsong Yang

Abstract Objective: We aimed to verify whether mechanical growth factor (MGF) may be an effective target for treating ankylosing spondylitis. Methods: FOXP3 expression was measured in Treg cells from healthy male subjects administered MGF. A rat model of ankylosing spondylitis was established, and the level of ankylosing spondylitis-related factors (tumor necrosis factor [TNF]-α, interleukin [IL]-2, and IL-10) was measured. Results: We found that the proliferation and total number of Treg cells, as well as FOXP3 expression, significantly increased in the MGF-treated groups compared with those in the control. The level of inflammation, bone destruction, and new bone formation significantly decreased in rats treated with MGF compared with those in the control group. TNF-α expression significantly decreased, whereas the IL-2 and IL-10 levels significantly increased in the MGF group compared with those in the control. Conclusions: MGF may delay disease progression in ankylosing rats by inducing FOXP3 expression, promoting FOXP3+ Treg cell proliferation and differentiation, reducing TNF-α expression, and increasing IL-10 and IL-2 expression.


2019 ◽  
Vol 22 (4) ◽  
pp. 232-237 ◽  
Author(s):  
Jihong An

Objective: This study aims to investigate the expression and clinical significance of Th17 cells and related factors in peripheral blood of patients with Autoimmune Hepatitis (AIH). Methods: A retrospective selection of 100 patients with AIH were included as a study group, and 100 healthy volunteers in the outpatient clinic were selected as the control group. The levels of IL- 17, IL-6, IL-21 and TNF-α in peripheral blood of all subjects were detected by enzyme-linked immunosorbent assay and the frequency of Th17 cells and Treg cells was detected by flow cytometry. Results: Results showed that the study group had higher levels of serum total bilirubin (TBil), alkaline phosphatase (ALP), γ -glutamyltranspeptidase (γ-GT), immunoglobulin G (IgG), immunoglobulin M (IgM), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) than the control group, as well as higher levels of IL-17, IL-6, IL-21 and TNF-α in serum. The frequency of Th17 cells in peripheral blood was higher in the study group, while the frequency of Treg cells was lower. Also, serum IL-17, TNF-α levels and Th17 cells frequency were positively correlated with ALT and AST, whereas Treg cells frequency were negatively correlated with ALT and AST levels. Conclusion: Our finding demonstrates that Th17 cell frequency and their related factors IL-17 and TNF-α, are associated with liver damage, which might be used to monitor AIH disease severity.


Author(s):  
Theresia Indah Budhy ◽  
Ira Arundina ◽  
Meircurius Dwi Condro Surboyo ◽  
Anisa Nur Halimah

Abstract Objectives The purpose of this study is to analyze the effects of rice husk liquid smoke in Porphyromonas gingivalis-induced periodontitis in the inflammatory and proliferation marker such as nuclear factor kappa β (NF-kB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), transforming growth factor-β (TGF-β), fibroblast growth factor 2 (FGF2), collagen type 1 (COL-1) expression, and the number of macrophages, lymphocytes, and fibroblasts. Materials and Methods Rice husk liquid smoke is obtained by the pyrolysis process. Porphyromonas gingivalis-induced periodontitis in 20 μL phosphate-buffered saline containing 1 × 109 CFU was injected into the lower anterior gingival sulcus of Wistar rats. The periodontitis was then treated with 20 μL/20 g body weight of rice husk liquid smoke once a day for 2 and 7 days, respectively. After treatment, the bone and lower anterior gingival sulcus were analyzed with immunohistochemistry and hematoxylin–eosin staining. Results The treatment of periodontitis with rice husk liquid smoke showed a lower NF-kB, TNF-α, and IL-6 expression and a higher TGF-β, FGF2, and COL-1 expression than the control after treatment for 2 and 7 days (p < 0.05), respectively. The number of macrophages and fibroblasts was also higher when compared with the control group (p < 0.05), but the number of lymphocytes was lower than the control (p < 0.05). Conclusion Rice husk liquid smoke showed its effects on Porphyromonas gingivalis-induced periodontitis with a decrease in inflammatory markers and an increase in proliferation markers. The development of a rice husk liquid smoke periodontitis treatment is promising.


1991 ◽  
Vol 261 (4) ◽  
pp. G669-G676 ◽  
Author(s):  
B. Daniele ◽  
A. Quaroni

To investigate the role of diamine oxidase (DAO) in the intestinal mucosa, we compared its expression with cell proliferation and differentiation in the human colon carcinoma cell line Caco-2. DAO synthesis was evaluated in subconfluent and confluent cultures and in the presence of epidermal growth factor (EGF), a polypeptide hormone known to have specific trophic effects on the small intestinal mucosa. EGF stimulated DNA synthesis, significantly increased cellular DAO activity and the amount of enzyme secreted into the culture medium, but decreased expression of dipeptidyl peptidase IV, a marker of cell differentiation in confluent Caco-2 cells. Immunoprecipitation of DAO from cells labeled metabolically with [35S]methionine failed to demonstrate an increased enzyme synthesis in EGF-treated cells, suggesting that this hormone acted primarily at a posttranslational level by reducing DAO degradation before intracellular storage or secretion. A possible relationship between changes in cellular DAO activity and cell proliferation was also investigated by using aminoguanidine, a specific and potent DAO inhibitor. Although DAO activity was markedly suppressed, aminoguanidine had no significant effects on the rate of DNA synthesis. These results demonstrated that in Caco-2 cells EGF stimulated DNA synthesis and DAO expression; however, cell proliferation and differentiation were not correlated with the levels of cellular DAO, suggesting that this enzyme does not play a major role in the regulation of intestinal epithelial cell turnover.


1998 ◽  
Vol 274 (5) ◽  
pp. G863-G870 ◽  
Author(s):  
Adhip P. N. Majumdar ◽  
James R. Goldenring

In Fischer 344 rats, induction of gastric mucosal proliferative activity, whether the result of aging or injury or occurring after administration of epidermal growth factor, gastrin, or bombesin, is associated with a rise in tyrosine kinase activity and tyrosine phosphorylation of several mucosal proteins, including a protein with a molecular mass of 53–55 kDa. We hypothesized that this phosphotyrosine membrane protein (referred to as pp55) may play a role in regulating gastric mucosal cell proliferation and differentiation. Purification and subsequent immunoprecipitation studies now show that pp55 is a tyrosine kinase. In addition, the enzyme activity in the gastric mucosa is found to be fourfold higher in aged rats than in young rats. Incubation of gastric mucosal membranes with transforming growth factor-α (2 × 10−8 M) stimulates tyrosine kinase activity of pp55. Immuolocalization studies reveal that pp55 immunoreactivity is predominantly present in mucous cells that are located just above the proliferative zone and spasmolytic peptide-immunoreactive mucous neck cells. Tyrosine kinase activity as well as expression of pp55 are also greatly increased in the gastric mucosa after hypertonic saline-induced injury, a condition that results in stimulation of surface mucosal cell proliferation and differentiation. Our current data suggest that pp55 is a tyrosine kinase, likely localized to pre-surface cells. The presence of pp55 in pre-surface mucous cells and the expression and tyrosine kinase activity of this protein, which can be stimulated during mucosal cell proliferation and differentiation, strongly suggest a role for pp55 in differentiation of gastric surface mucous cells.


Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3120
Author(s):  
Ji Min Kim ◽  
Jun Ho Ji ◽  
Young Saing Kim ◽  
Suee Lee ◽  
Sung Yong Oh ◽  
...  

The mechanisms of epidermal growth factor (EGF) affecting EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF’s positive effects. Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). As a result, rhEGF increased EGFR and pEGFR expression. Furthermore, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. In addition, rhEGF bound to EGFR after than cetuximab, but cetuximab bound to EGFR more strongly than rhEGF. Moreover, expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRI-treated tissue. However, in rhEGF and EGFRI co-treated tissue, those expressions were increased. Expression of IL-1α, IL-8, and TNF-α was increased by EGFRIs and down-regulated by rhEGF. Furthermore, hBD-2 and hBD-3 protein expressions were inhibited by cetuximab or gefitinib treatment, and those decrements were increased by rhEGF treatment. In patients’ tissue evaluation, compared with controls, patients’ Ki-67 and EGFR expression were decreased (p = 0.015, p = 0.001). Patients’ IL-17 and TNF-α expression intensity was higher than that of the control group (p = 0.038, p = 0.037). After treatment with EGF ointment, average values of Ki-67, EGFR, and Melan-A were changed to normal values. Oppositely, patients’ proportions of IL-17 and TNF-α were decreased to low stain level. In conclusion, treatment of rhEGF improved EGFRI-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sam W. Z. Olechnowicz ◽  
Megan M. Weivoda ◽  
Seint T. Lwin ◽  
Szi K. Leung ◽  
Sarah Gooding ◽  
...  

Abstract Interactions between multiple myeloma (MM) and bone marrow (BM) are well documented to support tumour growth, yet the cellular mechanisms underlying pain in MM are poorly understood. We have used in vivo murine models of MM to show significant induction of nerve growth factor (NGF) by the tumour-bearing bone microenvironment, alongside other known pain-related characteristics such as spinal glial cell activation and reduced locomotion. NGF was not expressed by MM cells, yet bone stromal cells such as osteoblasts expressed and upregulated NGF when cultured with MM cells, or MM-related factors such as TNF-α. Adiponectin is a known MM-suppressive BM-derived factor, and we show that TNF-α-mediated NGF induction is suppressed by adiponectin-directed therapeutics such as AdipoRON and L-4F, as well as NF-κB signalling inhibitor BMS-345541. Our study reveals a further mechanism by which cellular interactions within the tumour-bone microenvironment contribute to disease, by promoting pain-related properties, and suggests a novel direction for analgesic development.


2020 ◽  
Vol 19 (4) ◽  
pp. 749-754
Author(s):  
Cynthia Arsita ◽  
Taufiqurrachman Nasihun ◽  
Atina Hussaana

Background : UVB radiation responsible for the most important biological effects including Vitamin D3 synthesis and inflammation. UVB radiation are absorbed by 7-dehydrocholesterol in the plasma membrane of epidermal cells resulting in production of cis-previtamin D3. In the other hand, an exposure to UVB leads to cutaneous tissue inflammation modulates by TNF-α which also increases platelet activating factor. VEGF and PDGF induced by TNF-α during wound healing, characterized with angiogenesis and reephitalization. Furthermore, vitamin D plays a role in inflammation inhibition and upregulates growth factors. However, the study of the mechanism has not yet been thoroughly investigated. Methods: This study uses post test only group design, subjected wistar rats divided into four groups. Control group, non irradiated with UVB, and the other three groups, treated with graded UVB dose started with 1 MED (50 mJ/cm2), 2 MED (100mJ/cm2) and 3 MED (150 mJ/cm2) and investigated at 6, 12, 24 and 48 hours post UVB irradiation. Result : The serum level of vitamin D, VEGF and PDGF were increasing due to UVB dose addition. The highest level was reached at 6 hours post radiation using 3 MED, which gradually decrease up to 48 hours (p =0,000). The rise of vitamin D after UVB radiation, inhibit TNF-α induction in every dose accordant UVB dose addition and the lowest level is using 3 MED at 12 hours post radiation (p =0,000). TNF-α reach its highest level at 24 hours post radiation using 1 MED, it is related with the acute phase of inflammation. Conclusion : This study reveal that higher UVB irradiance increases vitamin D and inhibit TNF-α which also promotes VEGF and PDGF. Bangladesh Journal of Medical Science Vol.19(4) 2020 p.749-754


Sign in / Sign up

Export Citation Format

Share Document