scholarly journals Quantification of Cytokines in Lip Tissue from Infants Affected by Congenital Cleft Lip and Palate

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 140
Author(s):  
Māra Pilmane ◽  
Nityanand Jain ◽  
Shivani Jain ◽  
Ilze Akota ◽  
Juta Kroiča
Keyword(s):  
Transforming Growth Factor Beta ◽  
Cleft Lip ◽  
Transforming Growth Factor ◽  
Cleft Lip And Palate ◽  
Mucosal Damage ◽  
Interferon Γ ◽  
Strong Positive Correlation ◽  
Th1 Cell ◽  
Ifn Γ ◽  
Preferential Activation

Cleft lip and palate are amongst the most common congenital malformations worldwide presenting with variable manifestations. Previous research has been primarily focused on the genetical aspects of its complex and multifactorial etiology. In the present study, we investigated the role of cytokines as mediators of epithelial–mesenchymal crosstalk and local site inflammation in cleft affected infants. Lip material was obtained from 12 children aged before primary dentition who suffered from orofacial clefting. The quantification of 12 cytokines (Interleukin-2,4,5,6,10,12,13,17A, Tumor Necrosis Factor-α, Interferon-γ, Transforming Growth Factor beta-1 and Granulocyte-Colony Stimulating Factor) was done using ELISA. Nonparametric Spearman Rho was used to ascertain the correlation between the expression levels of different cytokines. A significantly strong positive correlation was found between IL-2 and IFN-γ coupled with an IL4/IFN-γ ratio favoring IFN-γ. These findings indicate a shift towards the preferential activation of the Th1 differentiation pathway. Further, a pathological reduction in TGFβ-1 levels was noted, which may contribute to mucosal damage. IL-6 was more highly correlated to IFN-γ and IL-12 indicating its potential proinflammatory role in cleft affected tissues. This preferential activation of Th1 cell differentiation and consistent expression of IL-2,6,13 and TNF-α in cleft patients may indicate certain underlying mechanisms for inflammation mediation at the site of clefting.

Characteristics of Neuropeptide-Containing Innervation, Tissue Remodeling, Growth, and Vascularity in Noses of Patients With Cleft Lip and Palate

2020 ◽  
Vol 57 (8) ◽  
pp. 948-956
Author(s):  
Evija Balode ◽  
Mara Pilmane
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Cleft Lip ◽  
Transforming Growth Factor ◽  
Cleft Lip And Palate ◽  
Transforming Growth Factor Β1 ◽  
Nerve Fibers ◽  
Strong Positive Correlation ◽  
Pgp 9.5 ◽  
Affected Tissue

Objective: To detect the appearance and distribution of factors regulating remodeling, innervation, growth, and vascularity of the nasal tissue affected by cleft lip and palate (CLP). Design: Morphological analysis of human tissue. Setting: Cleft and craniofacial center. Participants: Fifteen patients who underwent CLP rhinoplasty, 7 control patients. Interventions: Rhinoplasty. Main Outcome Measures: Immunohistochemistry was performed with protein gene product (PGP) 9.5, transforming growth factor β1 (TGFβ1), vascular endothelial growth factor (VEGF), cluster of differentiation 34 (CD34), matrix metalloproteinase 2 (MMP2), MMP9, and tissue inhibitor of metalloproteinase 2 (TIMP2). The results were evaluated semiquantitatively. Spearman rank order correlation coefficient and Mann-Whitney U test were used for statistical analysis. Results: Cleft lip and palate–affected tissue revealed dense and loose connective tissue, adipose cells, and hyaline cartilage, along with numerous CD34-positive endotheliocytes and regions of VEGF-positive neoangiogenesis. We observed moderate to numerous PGP 9.5-positive nerve fibers. Transforming growth factor β1, MMP2, MMP9, and TIMP2 were found in cartilage and connective tissue. Cleft lip and palate–affected tissue compared to control samples showed a statistically significant difference in PGP 9.5 ( P = .006), VEGF ( P = .001), MMP2 ( P = .002), MMP9 ( P = .013), and TIMP2 ( P < .001) expression. We observed a strong, positive correlation between VEGF and MMP9 ( P = .027; r S = 0.705). Conclusions: The moderate expression of TGFβ1 and increased distribution of VEGF, MMP2, MMP9, and TIMP2 demonstrate an active extracellular matrix remodeling and angiogenesis, performed by proteases. The cartilaginous septum of the nose is an example of balance between tissue degradation and its suppression, demonstrated by the relationship between MMPs and TIMPs and the presence of VEGF.

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 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.

Mesenchymal stromal cell plasticity and the tumor microenvironment

2017 ◽  
Vol 1 (5) ◽  
pp. 487-492
Author(s):  
Hee Joon Bae ◽  
Shutong Liu ◽  
Ping Jin ◽  
David Stroncek
Keyword(s):  
Tumor Microenvironment ◽  
Transforming Growth Factor ◽  
Critical Role ◽  
Tumor Infiltrating Lymphocytes ◽  
Transforming Growth Factor Β ◽  
Interferon Γ ◽  
Tnf Α ◽  
Ifn Γ ◽  
Factor Α ◽  
Infiltrating Lymphocytes

Mesenchymal stem cells or mesenchymal stromal cells (MSCs) are a multipotent, heterogeneous population of cells that play a critical role in wound healing and tissue regeneration. MSCs, found in the tumor microenvironment, support tumor growth through the production of angiogenic factors, growth factors and extracellular matrix proteins. They also have immunomodulatory properties, and since they produce indoleamine 2,3-dioxygenase (IDO), prostaglandin E2 (PGE2) and transforming growth factor β (TGF-β), they have been thought to have primarily immunosuppressive effects. However, their role in the tumor microenvironment is complex and demonstrates plasticity depending on location, stimulatory factors and environment. The presence of melanoma-activated tumor-infiltrating lymphocytes (TILs) has been shown to produce pro-inflammatory changes with TH1 (type 1T helper)-like phenotype in MSCs via activated-TIL released cytokines such as interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and interleukin-1α (IL-1α), while simultaneously producing factors, such as IDO1, which have been traditionally associated with immunosuppression. Similarly, the combination of IFN-γ and TNF-α polarizes MSCs to a primarily TH1-like phenotype with the expression of immunosuppressive factors. Ultimately, further studies are encouraged and needed for a greater understanding of the role of MSCs in the tumor microenvironment and to improve cancer immunotherapy.

scholarly journals Increased Levels of Candida albicans Mannan-Specific T-Cell-Derived Antigen Binding Molecules in Patients with Invasive Candidiasis

2006 ◽  
Vol 13 (4) ◽  
pp. 467-474 ◽  
Author(s):  
Jan Kosonen ◽  
Arto Rantala ◽  
Colin H. Little ◽  
Päivi Lintu ◽  
Pirjo-Riitta Harjamäki ◽  
...  
Keyword(s):  
Candida Albicans ◽  
T Cell ◽  
Mrna Expression ◽  
Transforming Growth Factor Beta ◽  
Invasive Candidiasis ◽  
Transforming Growth Factor ◽  
Peripheral Blood Lymphocytes ◽  
Cell Mediated Immunity ◽  
Antigen Binding ◽  
Ifn Γ

ABSTRACT In addition to cytokines, CD4+ T cells have been found to secrete soluble, T-cell-derived antigen binding molecules (TABMs). These antigen-specific immunoproteins are thought to have immunoregulatory properties in the suppression of cell-mediated immunity (CMI) because they often associate with interleukin-10 (IL-10) and transforming growth factor beta. Decreased CMI causes susceptibility to infections caused by organisms which are normally nonpathogenic. In this situation, e.g., Candida albicans saprophytism may develop into invasive candidiasis. The difficult diagnosis of invasive candidiasis is based on the findings obtained from blood cultures and with tissue biopsy specimens, with some additional diagnostic value gained by the detection of Candida albicans mannan antigenemia and antimannan antibodies. In the present study, Candida albicans mannan-specific TABM (CAM-TABM) levels in the sera of patients with invasive candidiasis (n = 11), Candida colonization (n = 11) and noncolonization (n = 10), recurrent vulvovaginal candidiasis (n = 30), and atopic eczema dermatitis syndrome (n = 59) and healthy controls (n = 30) were analyzed. For 14 participants, the effect of mannan stimulation on TABM production and gamma interferon (IFN-γ) and IL-4 mRNA expression by peripheral blood lymphocytes was also studied. It was demonstrated that CAM-TABM production was the highest in patients with invasive candidiasis and that CAM-TABM levels could distinguish Candida-colonized patients from noncolonized patients. In addition, the CAM-TABM level was directly related to mRNA expression for IL-4 but not IFN-γ. These results reinforce the view that TABMs are associated with decreased CMI, immunoregulation, and the T-helper cell 2-type immune response.

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