Th1 and Th2 Cytokines Activity during Transformation and Lymphoma Formation S...IOSRJAVS
Marek's disease virus (MDV), a highly transmissible cell-associated neuropathic oncogenic alphaherpes virus affecting poultry health, resulting in considerable economic losses in poultry industry worldwide.Until now MDV still emerging and re emerging causing great economic losses in chicken despite of intensive vaccination and management policy used in poultry farms. However, cytokines and its role in MD pathogenesis and immunity had been described by some workers under certain experimental conditions by using different MDV strains challenge, they need to be more clarified during the more progressive lymphoma transformation stage. The present study aimed to examine the transcriptional profiling of a panel of cytokines genes in the splenic tissues of special broiler Japanese chickens (70-80 days old) contracted natural infection with MDV despite of intensive care and vaccination policy adopted by HVT and CVI988/Rispene. SYBR Green-based, real-time (RT)-PCR protocol was used to quantitate cytokine mRNA in freshly collected spleen tissue of MDV infected and control chicken. Changes in the levels of spleen interleukins (IL) as IL-6, IL-10, IL- 18 and IL-12P35, IL-4, interferon-gamma (IFN-γ) and inducible nitric oxide synthase (iNOS) mRNA was determined. Relative Messenger RNA (mRNA) expression levels of the above mentioned genes, and β-actin as a reference gene, were achieved. The results of quantitative real-time PCR (qPCR) assays using revealed significant up regulation in the expression levels of IL-6, IL-10, IL-18, and IL-12P35). The changes in the mRNA levels of IL-4, IFN-γ and inducible nitric oxide synthesase (iNOS) were minimal and not significant in comparison to those in uninfected age-matched control chicken. In conclusion, these data strongly support the hypothesis that pro-inflammatory responses, including high levels of Th2 cytokines as IL-10 and other interleukins as IL-6, IL-18 and IL12-P35, may play a major role during MDV lymphoma transformation stage induced by MDV strain of high virulence. These cytokines may be involved in maintenance of MDV infection and lymphoma formation. On the other hand, Th1 cytokines as IFN-γ, and iNOS had no or minimal role in induction of MDV-specific immune response during MDV lymphoma transformation stage.
Th1 and Th2 Cytokines Activity during Transformation and Lymphoma Formation S...IOSRJAVS
Marek's disease virus (MDV), a highly transmissible cell-associated neuropathic oncogenic alphaherpes virus affecting poultry health, resulting in considerable economic losses in poultry industry worldwide.Until now MDV still emerging and re emerging causing great economic losses in chicken despite of intensive vaccination and management policy used in poultry farms. However, cytokines and its role in MD pathogenesis and immunity had been described by some workers under certain experimental conditions by using different MDV strains challenge, they need to be more clarified during the more progressive lymphoma transformation stage. The present study aimed to examine the transcriptional profiling of a panel of cytokines genes in the splenic tissues of special broiler Japanese chickens (70-80 days old) contracted natural infection with MDV despite of intensive care and vaccination policy adopted by HVT and CVI988/Rispene. SYBR Green-based, real-time (RT)-PCR protocol was used to quantitate cytokine mRNA in freshly collected spleen tissue of MDV infected and control chicken. Changes in the levels of spleen interleukins (IL) as IL-6, IL-10, IL- 18 and IL-12P35, IL-4, interferon-gamma (IFN-γ) and inducible nitric oxide synthase (iNOS) mRNA was determined. Relative Messenger RNA (mRNA) expression levels of the above mentioned genes, and β-actin as a reference gene, were achieved. The results of quantitative real-time PCR (qPCR) assays using revealed significant up regulation in the expression levels of IL-6, IL-10, IL-18, and IL-12P35). The changes in the mRNA levels of IL-4, IFN-γ and inducible nitric oxide synthesase (iNOS) were minimal and not significant in comparison to those in uninfected age-matched control chicken. In conclusion, these data strongly support the hypothesis that pro-inflammatory responses, including high levels of Th2 cytokines as IL-10 and other interleukins as IL-6, IL-18 and IL12-P35, may play a major role during MDV lymphoma transformation stage induced by MDV strain of high virulence. These cytokines may be involved in maintenance of MDV infection and lymphoma formation. On the other hand, Th1 cytokines as IFN-γ, and iNOS had no or minimal role in induction of MDV-specific immune response during MDV lymphoma transformation stage.
Vitiligo is an acquired organ specific autoimmune disease of unknown etiology characterized by white patches in the skin. The patho-physiology of this disease is characterized by loss of functional melanocytes associated with infiltration of reactive T cells and dendritic cells. So, there are many evidences support that autoimmunity has a great role in Vitiligo-pathogenesis. Many efforts were made in areas of Histopathology, Immunology, and molecular biology to solve vitiligo puzzle. However, no clear etiology was described. We tried here to review some histopathological findings that make strong evidences for the autoimmunity in this disease.
Activation of surrogate death receptor signalling triggers peroxynitrite depe...Saurabh Shekhar
includes information about cisplatin resistance cancer cells and their execution through peroxynitrite triggered apoptosis due to death signaling receptors basedon the findings of research article published in cell death and diseases.
Cure of HIV infection by CCR5 ∆32/ ∆32 stem cell transplantation
- Kristina Allers, Gero Hutter, Jorg Hofmann, Kathrin Rieger, Christoph Loddenkemper, Eckhard Thiel and Thomas Schneider
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...JohnJulie1
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...NainaAnon
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells. When studying the molecular mechanism, it was found that TRIM35 interacted with IRF5, promoting the ubiquitination and degradation of IRF5. In the clinical specimens of HCC, TRIM35 was negatively correlated with the expression of IRF5. These observations reveal the oncogenic function of IRF5 in the progression of HCC, suggesting that IRF5 is a promising target for the therapy of HCC.
Vitiligo is an acquired organ specific autoimmune disease of unknown etiology characterized by white patches in the skin. The patho-physiology of this disease is characterized by loss of functional melanocytes associated with infiltration of reactive T cells and dendritic cells. So, there are many evidences support that autoimmunity has a great role in Vitiligo-pathogenesis. Many efforts were made in areas of Histopathology, Immunology, and molecular biology to solve vitiligo puzzle. However, no clear etiology was described. We tried here to review some histopathological findings that make strong evidences for the autoimmunity in this disease.
Activation of surrogate death receptor signalling triggers peroxynitrite depe...Saurabh Shekhar
includes information about cisplatin resistance cancer cells and their execution through peroxynitrite triggered apoptosis due to death signaling receptors basedon the findings of research article published in cell death and diseases.
Cure of HIV infection by CCR5 ∆32/ ∆32 stem cell transplantation
- Kristina Allers, Gero Hutter, Jorg Hofmann, Kathrin Rieger, Christoph Loddenkemper, Eckhard Thiel and Thomas Schneider
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...JohnJulie1
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...NainaAnon
The IRF family of proteins involves in the tumor progression. However, but the functions of IRF5 in the tumorigenesis are largely unknown. Here, IRF5 was found to be up-regulated in hepatocellular carcinoma (HCC). Interfering with IRF5 inhibited the growth and tumorigenic ability of HCC cells. When studying the molecular mechanism, it was found that TRIM35 interacted with IRF5, promoting the ubiquitination and degradation of IRF5. In the clinical specimens of HCC, TRIM35 was negatively correlated with the expression of IRF5. These observations reveal the oncogenic function of IRF5 in the progression of HCC, suggesting that IRF5 is a promising target for the therapy of HCC.
IRF5 Promotes the Progression of Hepatocellular Carcinoma and is Regulated by...
CKRBSACI 2005 SM
1. PO 1021
ABSTRACT
Rationale: Chemokine receptors are involved in the recruitment of T
lymphocytes to sites of infection and inflammation. CCR4 and
CXCR3 expression has been associated with Th2 and Th1 immune
responses respectively. We examined the expression of the
chemokine receptors CCR4 and CXCR3 on CD3+ cells after allergen
and diluent challenge in the skin.
Methods: Skin biopsies were obtained from atopic allergic and non-
atopic individuals after allergen PPD and diluent challenge.
Biopsies were examined for CD3+CCR4+ cells and CD3+CXCR3+
cells using dual immunofluorescence and IL-4 and IFN-γ mRNA
expressing cells using in situ hybridisation.
Results: Following allergen challenge there was a significant
increase in CD3+/CCR4+ cell numbers within the atopic group
(p<0.001) and not in the non-atopics (p=0.28). Both atopics and non
atopics showed an increase in CD3+/CXCR3+ cells at 48 hours after
PPD challenge (p=0.01 and p=0.06 respectively). Furthermore IL-4
mRNA+ cells peaked at 8 hours after allergen challenge while IFNg
mRNA+ cells were elevated after PPD challenge at 48 hours, with no
change in the nonatopics.
Conclusion: These data suggest that, in vivo, in man CCR4 recruits
Th2 cells to the skin in the late response to specific allergen,
whereas CXCR3 recruits Th1 cells to the skin in response to PPD
challenge.
Figure 6: IL-4 mRNA and IFN-γ mRNA expressing
cells after (8hr & 48hr) allergen and PPD challenge
BACKGROUND
The recruitment of Th2 lymphocytes is recognised to play a
central role in the pathogenesis of allergic conditions.
Chemokine receptor expression on T cells has been shown to
control both their cellular arrest within the vascular
compartment through the up regulation of integrin molecules
and their subsequent migration within the extravascular space.
METHODS
Figure 3: CD3+expressing CCR4
(8 hr) after Ag and PPD challenge
CONCLUSIONS
Figure 7: Relationship between IL-4 mRNA & CCR4
expressing cells and IFN-γ mRNA & CXCR3 expressing
cells
PATIENTS
Sixteen atopics with summer hayfever, as defined by their history
and positive skin prick test (median 8.0mm, IQ (5, 10)) to grass
pollen were recruited to this study. The median age was 27 yrs (IQ,
24, 29) and M:F, 11:5. The serum concentrations of total IgE was
(median 171IU/L ( IQ 42, 720)) and allergen specific IgE 24.0 IU/L
(IQ 13, 79). Each subject underwent intradermal challenge to the
extensor surface of the forearms with Tuberculin PPD (10
Tuberculin Units in 0.02ml), allergen (10 Biological Units in 0.02ml
Phleum pratense or house dust mite extract) and diluent. The size of
the late phase response was recorded eight and 48 hours after
injection and a 4mm skin punch biopsy was taken under local
anaesthetic.
AIMS
To determine:
a) the expression of chemokine receptors CCR4 and CXCR3 on
CD3+ cells in the skin following allergen and PPD challenge
respectively
b) IL-4 and IFN-γ mRNA expressing cells as putative markers of
Th2 and Th1 cells, respectively
CCR4 and CXCR3 on CD3+ Cells in the Skin following allergen and PPD
challenge in atopic and non-atopic individuals
SC Martins, GK Banfield, H Watanabe, KT Nouri-Aria, K Furukido, CM Lloyd, DS Robinson SR Durham
Upper Respiratory Medicine, National Heart & Lung Institute, and Leukocyte Biology, Imperial College London, Manresa Road, London SW3 6LR, United Kingdom.
Allergen
Dil. 8 hrs 48 hrs
0
10
20
30
40
50
mRNA+cells/mm2
IL-4
IFN-γ
PPD
0
5
10
15
20
Dil. 8 hrs 48 hrs
mRNA+cells/mm2
IL-4
IFN-γ
CD3+
/CXCR3+
CD3+
/CCR4+
Dual staining
0
20
40
60
80
100
Ag8 PPD8 Ag48 PPD48
%CCR4+
CXCR3+
cells
%double
%CXCR3
%CCR4
-20 0 20 40 60 80
CXCR3 +ve cells/mm2
0
10
20
30
IFN-γmRNA+vecells/mm2
r=0.61
p=0.03
Skin (PPD 48)
0 20 40 60 80 100
CCR4 +ve cells/mm
2
0
20
40
60
80
100
IL-4mRNA+vecells/mm2
r=0.64
p=0.01
Skin (Ag8)
IL-4 mRNA vs CCR4 IFN-γ mRNA vs CXCR3
In a study of human cutaneous allergen-induced late responses (8hr) and tuberculin-induced
delayed responses (48) hr, in which each subject acted as his/her own control:
- CCR4 is increased on T cells at 8hr after allergen, correlates with IL-4 expression and is a
phenotypic marker of Th2 cells
- CXCR3 is increased on T cells at 48hrs after tuberculin challenge, correlates with IFN-γ
expression and is a phenotypic marker of Th1 cells
- These studies demonstrate that CCR4 is a potential therapeutic target for allergic diseases
in man
Table 1: CD3+/CCR4+, CD3+/CXCR3+ and cytokine mRNA expressing cells (IL-4 & IFN-γ)/mm2
Five micron acetone fixed sections were examined for the
proportion of CD3+CCR4+, CD3+CXCR3+ and the co-expression
of CCR4 and CXCR3 cells using dual immunofluorescence.
Six micron paraformaldehyde sections were used for detection
of IL-4 and IFN-γ mRNA expressing cells were determined by
In situ hybridisation.
STATISTICAL ANALYSIS
Figure 5: %CCR4+, CXCR3+ and CCR4+CXCR3+
cells (8hr & 48hr) after Ag and PPD challenge
The Mann-Whitney U test was used for comparison between
allergen and PPD challenge. Wilcoxon Matched-pairs signed-
rank test was used for within subject analysis. The Spearman
rank test was used to correlate the numbers of IL-4 mRNA
expressing cells with CCR4+ cells and IFN-γ mRNA expressing
cells with CXCR3+ cells ACKNOWLEDGMENT
This work is sponsored by Imperial College Trust Fund with the support of GlaxoSmithKline
Figure 1: Skin section demonstrating
CD3+CCR4+ cells (Ag 8hr)
Figure 2: Skin section demonstrating
CD3+CXCR3+ cells (PPD 48hr)
Figure 4: CD3+expressing CXCR3
(48 hr) after Ag and PPD challenge
Dil. Ag
(8hr)
Ag
(48hr)
P
values
Dil. PPD
(8hr)
PPD
(48hr)
P
values
CD3+
/CCR4+
cells
7.6±1.4 40.5±6*** 35±9.5** 0.000
0.009
18.7±7.7 7.7±1.6 53.8±13.6* 0.02
CD3+
/CXCR3+
cell
0.5±0.26 2.5±0.75* 0.8±0.45 0.04
0.7
3.9±3.4 1.3±0.47 20±5.6* 0.01
0.4
IL-4 mRNA+
cells
1.0±0.53 36.9±10.8* 19.9±8.5* 0.001 1.65±0.8 1.88±1.2 2.68±1.4 0.9
0.6
IFN-γ mRNA+
cells
0.57±0.2 6.5±1.1* 5.5±0.9* 0.001
0.001
0.44±0.2 1.7±0.5* 10.3±2.3** 0.03
0.003
Data are shown as mean±SEM
Dil 48hr
Ag
0
10
20
30
CD3+/CXCR3+cells/mm
2
Dil 48hr
PPD
p=0.7 p=0.03
p=002
(74)
(57)
(57)
(55)
Dil 8hr
Ag
0
20
40
60
80
100
CD3+/CCR4+cells/mm
2
Dil 8hr
PPD
p=0.0000 p=0.1
p=0.000
(126)