scholarly journals STAT6 regulates natural helper cell proliferation during lung inflammation initiated by Alternaria

2012 ◽  
Vol 303 (7) ◽  
pp. L577-L588 ◽  
Author(s):  
Taylor A. Doherty ◽  
Naseem Khorram ◽  
Jinny E. Chang ◽  
Hee-Kyoo Kim ◽  
Peter Rosenthal ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Human Peripheral Blood ◽  
Constitutive Expression ◽  
Helper Cell ◽  
Th2 Cytokines ◽  
Specific Sequence ◽  
Ki 67 ◽  
Rapid Induction ◽  
Natural Helper ◽  
Fungal Allergen

Asthma exacerbations can be caused by a number of factors, including the fungal allergen Alternaria, which is specifically associated with severe and near-fatal attacks. The mechanisms that trigger lung responses are unclear and might vary between allergens. A comparison between Alternaria, Aspergillus, Candida, and house dust mite, all allergens in humans, showed that only Alternaria promoted immediate innate airway eosinophilia within 12 h of inhalation in nonsensitized mice. Alternaria, but not the other allergens, induced a rapid increase in airway levels of IL-33, accompanied by IL-33 receptor (IL-33R)-positive natural helper cell (NHC) production of IL-5 and IL-13. NHCs in the lung and bone marrow constitutively expressed transcription factors [GATA-3 and E26 transformation-specific sequence-1 (ETS-1)] that could allow for rapid induction of T helper type 2 (Th2) cytokines. Lung NHC numbers and proliferation (%Ki-67), but not IL-5 or GATA-3 expression, were significantly reduced in STAT6-deficient mice 3 days after one challenge with Alternaria. Alternaria induced NHC expression of the EGF receptor ligand amphiregulin (partially dependent on STAT6), as well as EGF receptor signaling in the airway epithelium. Finally, human peripheral blood NHCs (CRTH2+CD127+ lineage-negative lymphocytes) from allergic individuals highly expressed GATA-3 and ETS-1, similar to lung NHCs in mice. In summary, Alternaria-induced lung NHC proliferation and expression of amphiregulin are regulated by STAT6. In addition, NHCs in mouse and humans are primed to express Th2 cytokines through constitutive expression of GATA-3 and ETS-1. Thus several transcription factor pathways (STAT6, GATA-3, and ETS-1) may contribute to NHC proliferation and Th2-type responses in Alternaria-induced asthma.

T helper cell unresponsiveness: Rapid induction in antigen-transgenic and reversion in non-transgenic mice

1994 ◽  
Vol 24 (12) ◽  
pp. 2966-2973 ◽  
Author(s):  
Martin F. Bachmann ◽  
Urs Hoffmann Rohrer ◽  
Ulrich Steinhoff ◽  
Kurt Bürki ◽  
Susan Skuntz ◽  
...  
Keyword(s):  
Transgenic Mice ◽  
T Helper Cell ◽  
Helper Cell ◽  
T Helper ◽  
Rapid Induction

scholarly journals rhEGF Treatment Improves EGFR Inhibitor-Induced Skin Barrier and Immune Defects

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3120
Author(s):  
Ji Min Kim ◽  
Jun Ho Ji ◽  
Young Saing Kim ◽  
Suee Lee ◽  
Sung Yong Oh ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Skin Barrier ◽  
Control Group ◽  
Ki 67 ◽  
Positive Effects ◽  
Egfr Expression ◽  
Tnf Α ◽  
Proliferation And Differentiation ◽  
Gefitinib Treatment ◽  
Immune Defects

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.

Ki-67, p53, Bcl-2, TGF-α and EGF receptor expression in rectal carcinoid tumors

1998 ◽  
Vol 114 ◽  
pp. A1180
Author(s):  
T. Shimizu ◽  
S. Tanaka ◽  
K. Haruma ◽  
T. Tanimoto ◽  
M. Kunihiro ◽  
...  
Keyword(s):  
Egf Receptor ◽  
Carcinoid Tumors ◽  
Receptor Expression ◽  
Rectal Carcinoid ◽  
Ki 67

Role of epidermal growth factor (EGF) and its receptor in the development of the human placenta

1995 ◽  
Vol 7 (6) ◽  
pp. 1465 ◽  
Author(s):  
T Maruo ◽  
H Matsuo ◽  
T Otani ◽  
M Mochizuki
Keyword(s):  
Egf Receptor ◽  
Placental Lactogen ◽  
Immunocytochemical Staining ◽  
Placental Development ◽  
Ki 67 ◽  
Serum Free ◽  
C Cell ◽  
Serum Free Condition ◽  
And Function

To elucidate the role of EGF in human placental development, effects of EGF on the proliferation and differentiation of trophoblasts were investigated. Explants of trophoblastic tissues obtained from 4-5 week or 6-12 week placentas were, respectively, cultured with or without EGF, in the presence or absence of triiodo-L-thyronine (T3) in a serum-free condition. The proliferative activity was examined by immunocytochemical staining with an antibody Ki-67, and the differentiated function was assessed by the ability to secrete human chorionic gonadotrophin (hCG) and human placental lactogen (hPL). In 4-5 week placentas, EGF and EGF receptor were localized in cytotrophoblast (C-cell), and EGF augmented the proliferation of C-cell without affecting the ability to secrete hCG and hPL. In contrast, in 6-12 week placentas, EGF and EGF receptor were localized in syncytiotrophoblast (S-cell), and EGF stimulated the secretion of hCG and hPL without affecting the proliferation of C-cell. In situ hybridization with c-erb B probe revealed that c-erb B mRNA is expressed in the S-cell after 6 weeks' gestation. Column chromatography of the serum-free media obtained by 5-day culture of early placental tissues resulted in the elution of immunoreactive EGF. The addition of T3 (10(-8) mol L(-1)) resulted in increased secretion of immunoreactive EGF by placental explants. These findings suggest that EGF acts as an autocrine factor in regulating early placental growth and function in synergy with thyroid hormone.

scholarly journals c-maf Promotes T Helper Cell Type 2 (Th2) and Attenuates Th1 Differentiation by Both Interleukin 4–dependent and –independent Mechanisms

1998 ◽  
Vol 188 (10) ◽  
pp. 1859-1866 ◽  
Author(s):  
I-Cheng Ho ◽  
David Lo ◽  
Laurie H. Glimcher
Keyword(s):  
Transgenic Mice ◽  
Ectopic Expression ◽  
T Helper Cell ◽  
Helper Cell ◽  
Th2 Cytokines ◽  
Cell Type ◽  
T Helper ◽  
Helper Cell Type

The c-maf protooncogene is a T helper cell type 2 (Th2)-specific transcription factor that activates the interleukin (IL)-4 promoter in vitro. Although it has been postulated that c-maf directs the Th2-specific expression of the IL-4 gene in vivo, direct evidence that c-maf functions during the differentiation of normal, primary T cells is lacking. We now demonstrate that overexpression of c-maf in vivo skews the Th immune response along a Th2 pathway, as evidenced by increased production of Th2 cytokines and the IL-4–dependent immunoglobulins, IgG1 and IgE. The overproduction of IgGl and IgE in the CD4 promoter/c-maf transgenic mice was IL-4 dependent since this was not observed in c-maf transgenic mice bred onto an IL-4–deficient background. Ectopic expression of c-maf in mature Th1 cells did not confer on them the ability to produce IL-4, but did decrease the production of IFN-γ. The attenuation of Th1 differentiation by c-maf overexpression occurred by a mechanism that was independent of IL-4 and other Th2 cytokines, and could be overcome by IL-12. These studies demonstrate that c-maf promotes Th2 differentiation by IL-4–dependent mechanisms and attenuates Th1 differentiation by Th2 cytokine-independent mechanisms.

scholarly journals Suppressors of Cytokine Signaling 3 Expression in Eosinophils: Regulation by PGE2and Th2 Cytokines

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Esther López ◽  
María Paz Zafra ◽  
Beatriz Sastre ◽  
Cristina Gámez ◽  
Mar Fernández-Nieto ◽  
...  
Keyword(s):  
Human Peripheral Blood ◽  
Th2 Cells ◽  
Cytokine Signaling ◽  
Prostaglandin E ◽  
Th2 Cytokines ◽  
Eosinophilic Bronchitis ◽  
Socs Proteins ◽  
Suppressors Of Cytokine Signaling ◽  
Blood Eosinophils ◽  
Socs3 Protein

Asthma and nonasthmatic eosinophilic bronchitis (NAEB) are respiratory disorders characterized by a predominance of Th2 cells and eosinophilic inflammation. Suppressors of cytokine signaling (SOCS) proteins play an important role in Th2-mediated allergic responses through control of the balance between Th1 and Th2 cells, particularly, SOCS3 and SOCS5. The aim of this study was to analyze SOCS expression in human peripheral blood eosinophils from patients with asthma, NAEB and healthy controls. SOCS expression in eosinophils from subjects was demonstrated by different techniques. Results showed that expression of SOCS3 in eosinophils and CD4 T cells from patients was higher than in healthy subjects. In addition, we demonstrated that prostaglandin E2(PGE2) and Th2 cytokines are able to upregulate SOCS3 production in eosinophils and attenuate its degranulation. In conclusion, eosinophils are able to transcribe and translate SOCS3 protein and can contribute to the regulation of the Th1/Th2 balance through SOCS3 production.

scholarly journals Further Analysis of Interleukin-2 Receptor Subunit Expression on the Different Human Peripheral Blood Mononuclear Cell Subsets

Blood ◽  
1998 ◽  
Vol 91 (1) ◽  
pp. 165-172 ◽  
Author(s):  
Denis David ◽  
Lynda Bani ◽  
Jean-Louis Moreau ◽  
Christophe Demaison ◽  
Karine Sun ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Peripheral Blood Mononuclear Cell ◽  
Mononuclear Cell ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Interleukin 2 ◽  
Constitutive Expression ◽  
Variable Intensity ◽  
Peripheral Blood Mononuclear ◽  
Interleukin 2 Receptor

We have investigated the expression of the three components of the interleukin-2 receptor (IL-2Rα, IL-2Rβ, and IL-2Rγ) on the surface of the various peripheral blood mononuclear cell (PBMC) subsets by flow cytometry analysis. The PBMC were immediately isolated (ficoll) from blood collected on heparin as anticoagulant. The three IL-2R components are absent or only marginally detectable on CD4 T lymphocytes. No expression of the IL-2R chains is found for the B lymphocytes. In most donors, the three chains are not detectable on CD8 T lymphocytes, but for a few of them, IL-2Rβ or IL-2Rγ are clearly expressed. CD56 high (IL-2Rα+) and CD56 low (IL-2Rα−) natural killer (NK) cells express IL-2Rβ, but not IL-2Rγ. IL-2Rγ is expressed by monocytes of all donors although with variable intensity. When blood is collected on other anticoagulants or when cells are isolated 1 day after collection, IL-2Rα, IL-2Rβ, and IL-2Rγ are largely expressed on the surface of most PBMC. This observation provides a possible explanation for divergent data previously reported on IL-2R expression. Finally, we show that IL-2Rγ, which is not detectable on the cell surface of lymphocytes, is nevertheless expressed and stored as an intracellular component. This result is in agreement with the constitutive expression of the IL-2Rγ gene and suggests a specific regulatory mechanism for IL-2Rγ membrane translocation.

scholarly journals rhEGF Treatment Improves EGFR Inhibitors-Induced Skin Barrier and Immune Defects

2020 ◽  
Author(s):  
Ji Min Kim ◽  
Jun Ho Ji ◽  
Young Saing Kim ◽  
Suee Lee ◽  
Sung Yong Oh ◽  
...  
Keyword(s):  
Inflammatory Cytokines ◽  
Egf Receptor ◽  
Skin Barrier ◽  
Control Group ◽  
Ki 67 ◽  
Western Blot Assay ◽  
Positive Effects ◽  
Egfr Expression ◽  
Tnf Α ◽  
Proliferation And Differentiation

Abstract Background: The mechanisms of epidermal growth factor (EGF) effects EGF receptor inhibitor (EGFRI)-related skin toxicities are as yet unknown. We investigated which mechanisms are involved in EGF’s positive effects. Methods: Two types of EGFRIs, cetuximab and gefitinib, were used to treat the cells or 3d-cultured human skin tissue with recombinant human EGF (rhEGF). The expression levels of skin barrier related proteins, inflammatory cytokines, and antimicrobial peptides (AMPs) were measured by using RT qPCR, ELISA, immunohistochemical (IHC) stain, or immunofluorescence..Results: Using western blot assay, cetuximab decreased EGFR and phosphorylated EGFR (pEGFR) expression. In contrast, rhEGF increased EGFR and pEGFR expression. Also, rhEGF induces EGFR signaling by pAKT and pPI3K expression in gefitinib and rhEGF co-treated cells. Expressions of proliferation and differentiation proteins, both ki-67 and filaggrin, were decreased in EGFRIs -treated tissue. However, in rhEGF and EGFRIs co-treated tissue, those expressions were increased. Pro-inflammatory cytokines, including IL-1α, IL-8, and TNF-α expression, were increased by EGFRIs, and down-regulated by rhEGF. In patients’ tissue evaluation, compared with control, 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 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.Conclusions: Treatment of rhEGF improved EGFRIs-induced skin eruption via normalizing the proliferation and differentiation of keratinocytes, reducing inflammatory cytokines by the affected EGFRIs.

scholarly journals Constitutive expression of pore-forming protein in peripheral blood gamma/delta T cells: implication for their cytotoxic role in vivo.

1990 ◽  
Vol 172 (6) ◽  
pp. 1877-1880 ◽  
Author(s):  
M Nakata ◽  
M J Smyth ◽  
Y Norihisa ◽  
A Kawasaki ◽  
Y Shinkai ◽  
...  
Keyword(s):  
T Cells ◽  
Cytotoxic Activity ◽  
Peripheral Blood ◽  
Human Peripheral Blood ◽  
Constitutive Expression ◽  
Immunocytochemical Staining ◽  
Target Cells ◽  
Gamma Delta T Cells ◽  
Gamma Delta

The cytotoxic activity and pore-forming protein (PFP) expression of human peripheral blood (PB) gamma/delta T cells were examined. Fresh gamma/delta T cells isolated from PB lymphocytes by fluorescence-activated cell sorting exhibited a substantial natural killer-like cytotoxic activity against K562 target cells and had a high cytotoxic potential triggered by anti-CD3 monoclonal antibody (mAb) against P815 target cells bearing Fc gamma R. Immunocytochemical staining with an anti-PFP mAb revealed that virtually all PB gamma/delta T cells are granular lymphocytes with abundant PFP in their cytoplasmic granules. Constitutive expression of PFP in PB gamma/delta T cells was also demonstrated by Northern blot analysis. These observations support the proposed role of gamma/delta T cells in cytolytic immune surveillance in vivo.

Transforming growth factor-α, epidermal growth factor receptor, and proliferating potential in benign and malignant gliomas

1991 ◽  
Vol 75 (1) ◽  
pp. 97-102 ◽  
Author(s):  
Motohiko Maruno ◽  
John S. Kovach ◽  
Patrick J. Kelly ◽  
Takehiko Yanagihara
Keyword(s):  
Growth Factor ◽  
Epidermal Growth Factor ◽  
Egf Receptor ◽  
Transforming Growth Factor ◽  
Malignant Gliomas ◽  
Proliferation Index ◽  
Ki 67 ◽  
Content Type ◽  
Transforming Growth Factor Α ◽  
Epidermal Growth

✓ Surgical specimens from six benign and 16 malignant human gliomas were investigated immunohistochemically to correlate the degree of malignancy, the distribution of transforming growth factor-alpha (TGF-α) and epidermal growth factor (EGF) receptor, and the potential for cell proliferation using monoclonal antibodies to TGF-α, EGF receptor, and Ki-67. Fourteen (88%) of the malignant gliomas and one (17%) of the benign gliomas were found to be positive for TGF-α, and 14 (88%) of the malignant gliomas and two (33%) of the benign gliomas expressed EGF receptor. The proliferation index with Ki-67 was 18.8% ± 8.1% (mean ± standard deviation) in malignant gliomas and 1.9% ± 1.8% in benign gliomas. In general, cells positive for EGF receptor and Ki-67 were randomly distributed throughout the tumor tissue, and cells positive for TGF-α tended to be clustered without obvious relationship to areas of necrosis or blood vessels. In some tumors, cells positive for TGF-α, EGF receptor, and Ki-67 were associated in a focal distribution. The more frequent expression of TGF-α and EGF receptor in the highly proliferative malignant gliomas is compatible with a role for TGF-α and EGF receptor in the induction or stimulation of malignant gliomas.

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