1. Interleukin-13 inhibits cytokines synthesis by blocking nuclear factor-κB and
c-Jun N-terminal kinase in human mesangial cells. J Biomed Res, 2010;
24(4):308-316
Chunhua Zhua,b, Aihua Zhanga,b, Songming Huanga,b, Guixia Dinga,b, Xiaoqin Panb,
Ronghua Chenb
a
Nanjing Children's Hospital Affiliated to Nanjing Medical University, Nanjing,
Jiangsu 210008, China;
b
Institute of Pediatrics, Nanjing Medical University, Nanjing, Jiangsu 210029,
China.
Abstract: Objective: Monocytes/macrophages, proinflammatory cytokines and
chemokines are important in the pathogenesis of glomerulonephritis. Interleukin (IL)
-13 has been shown to exert potent anti-inflammatory properties. This study was
designed to investigate the effect of IL-13 on the expression of proinflammatory
cytokines, chemokines and profibrogenic cytokines and the involved molecular
mechanism in cultured human mesangial cells (HMCs). Methods: The expressions of
proinflammatory cytokines, chemokines and profibrogenic cytokines were determined
by ribonuclease protection assay (RPA). Activity of nuclear factor-kappa B (NF-κB)
and activator protein-1 (AP-1) was examined by electrophoretic mobility shift assay
(EMSA). NF-κB subunit p65 nuclear transportation and c-Jun N-terminal kinase
(JNK) activity were assayed by immunoblot. Results: Recombinant IL-13 inhibited
tumor necrosis factor-α (TNF-α), IL-1α, IL-1β, monocyte chemoattractant protein-1
(MCP-1), IL-8, and transforming growth factor-β1 (TGF-β1) mRNA expressions in a
dose-dependent manner. Lipopolysacchorides (LPS) dramatically increased NF-κB
DNA binding activity of HMCs, which was inhibited by IL-13 in a dose-dependent
manner. LPS-activated NF-κB contained p50 and p65 dimers, but not c-Rel subunit.
IL-13 blocked LPS-induced NF-κB subunit p65. LPS stimulated JNK/AP-1 activation,
which was inhibited by IL-13 in a dose-dependent manner. Conclusion: IL-13 inhibits
proinflammatory cytokines, chemokines, and profibrogenic cytokines synthesis by
blocking NF-κB and JNK/AP-1 activation. These observations point to the
importance of IL-13 in the modulation of inflammatory processes in the renal
glomerulus.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR100408&flag=1
2. A functional type I interferon pathway drives resistance to cornea herpes
simplex virus type 1 infection by recruitment of leukocytes. J Biomed Res,
2011; 25(2):111-119
Christopher D. Conradya, Heather Jonesa, Min Zhengb, Daniel J.J. Carra,b
a
Departments of Microbiology, Immunology, and bOphthalmology, The University
of Oklahoma Health Science Center, Oklahoma City, OK 73104, USA.
Abstract: Type I interferons are critical antiviral cytokines produced following herpes
simplex virus type-1 (HSV-1) infection that act to inhibit viral spread. In the present
study, we identify HSV-infected and adjacent uninfected corneal epithelial cells as the
source of interferon-α. We also report mice deficient in the A1 chain of the type I IFN
receptor (CD118-/-) are extremely sensitive to ocular infection with low doses (100
PFU) of HSV-1 as seen by significantly elevated viral titers in the cornea compared to
wild type (WT) controls. The enhanced susceptibility correlated with a loss of CD4+
and CD8+ T cell recruitment and aberrant chemokine production in the cornea despite
mounting an adaptive immune response in the draining mandibular lymph node of
CD118-/- mice. Taken together, these results highlight the importance of IFN
production in both the innate immune response as well as eliciting chemokine
production required to facilitate adaptive immune cell trafficking.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr110204&flag=1
3. mRNA profiles of cytokine receptors in unstimulated peripheral blood
mononuclear cells from patients with chronic idiopathic urticaria. J Biomed
Res, 2011; 25(2):141-147
Jianming Gaoa,c, Aizhen Yangb, Min Chenc, Ansheng Lic, Xu Yaoc, Yumei Lic, Shihai
Xiec, Xueyuan Yangc, Liansheng Zhongc, Zhiqiang Chenc
a
Department of Dermatology, Haidian Hospital, Beijing 10080, China;
b
Oncology Center of Chinese PLA 81 st Hospital, Nanjing 210002, Jiangsu, China;
c
Section of Clinical Immunology, Institute of Dermatology, Chinese Academy of
Medical Sciences & Peking Union Medical College, Nanjing 210042, Jiangsu,
China.
Abstract: This present study was aimed to investigate the roles of the receptors of
Th1/Th2 cytokines and chemokines in the pathogenesis of chronic idiopathic urticaria
(CIU). Thirty patients with CIU, 30 patients with dermographism and 30 healthy
controls were randomly enrolled. Reverse transcription-PCR (RT-PCR) was used to
analyze the mRNA of cytokine receptors in peripheral blood mononuclear cells
(PBMCs). The mRNA levels of tumor necrosis factor receptor (TNFR), interferon-γ
receptor (IFN-γR), and interleukin-10 receptor (IL-10R) were statistically increased in
the CIU group (P < 0.05), while IL-2R, IL-4R, IL-6R, and IL-13R showed no significant
differences between the CIU and other groups. The mRNA levels of CCR3 and CCR6
were statistically increased in the CIU group (P < 0.05). The toll-like receptor 2 (TLR2)
mRNA level was significantly lower in the CIU group than the healthy control group
(P < 0.05). These findings indicate that the regulation of mRNA of TNFR, IFN-γR,
IL-10R, CCR3, CCR6 and TLR2 may be involved in the pathogenesis of CIU.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr110208&flag=1
4. TLR2 was overexpressed independent of IL-6 in patients with valvular atrial
fibrillation. J Biomed Res, 2011; 25(3):178-184
Jian Wanga, Lei Xuea, Hailong Caoa, Fei Cuia, Ting Daib, Yijiang Chena
a
Department of Thoracic and Cardiovascular Surgery, the First Affiliated Hospital
of Nanjing Medical University, Nanjing, Jiangsu 210029, China;
b
Department of Pharmacology, Nanjing Medical University, Nanjing, Jiangsu
210029, China.
Abstract: Toll-like receptor 2 (TLR2) has recently been shown to be up-regulated in
patients with non-valvular atrial fibrillation (AF). The present study was aimed to
determine whether the pathogenesis and development of AF is associated with the
up-regulation of TLR2. Clinical data and right atrial appendage (RAA) specimens
were collected from 20 patients with persisten AF (PeAF), 15 patients with
paroxysmal AF (PaAF) and 13 patients with no history of AF undergoing valvular
replacement. The results showed that gene expression and protein content of TLR2
were increased in both the AF subgroups, compared with the sinus rhythm (SR) group.
Between the two AF subgroups, PaAF had a higher TLR2 level than PeAF. However,
no difference in interluekin (IL)-6 content was found among the three groups, and no
correlation was found between TLR2 and IL-6 in PeAF patients (r = 0.090, P = 0.706),
PaAF patients (r = 0.408, P = 0.131) and AF patients (r = -0.301, P = 0.079).
Immunohistochemical analysis revealed that TLR2 was distributed in RAAs of AF
patients and confirmed the immunoblotting results. In conclusion, we demonstrated
that TLR2 was elevated in AF (especially PaAF) patients with valvular heart disease,
further implicating inflammation involved in the pathogenesis and development of
AF.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=jbr110304&flag=1
5. Effects of lysed Enterococcus faecalis FK-23 on experimental allergic rhinitis
in a murine model. J Biomed Res, 2012; 26(3):226-234
Luping Zhua, Takashi Shimadab,c, Ruoxi Chena, Meiping Lua, Qingzhao Zhanga,
Wenmin Lua, Min Yina,b, Tadao Enomotod, Lei Chenga,b
a
Department of Otorhinolaryngology, the First Affiliated Hospital, Nanjing Medical
University, Nanjing, Jiangsu 210029, China;
b
International Centre for Allergy Research, Nanjing Medical University, Nanjing,
Jiangsu 210029, China;
c
Central Research Laboratories, Nichinichi Pharmaceutical Corporation Ltd, Mie
518-1417, Japan;
d
NPO Japan Health Promotion Supporting Network, Wakayama 640-8558, Japan.
Abstract: In the current study, we sought to investigate whether lysed Enterococcus
faecalis FK-23 (LFK), a heat-killed probiotic preparation, attenuated eosinophil influx
into the upper airway and had immunomodulatory activity in a murine allergic rhinitis
model. Eighteen BALB/c mice were divided into three groups; the ovalbumin
(OVA)-sensitized/challenged group, which received saline orally for 6 weeks (OVA
group), the OVA-sensitized/challenged group, which received LFK orally for 6 weeks
(LFK-fed group), and the non-sensitized group, which received saline for 6 weeks
(saline control group). Nasal rubbing and sneezing were monitored during the study.
After the final challenge, interleukin (IL)-4, interferon (IFN)-γ, and OVA-specific IgE
levels in the sera and splenocyte culture supernatants were determined, eosinophilic
infiltrate into the upper airway was quantified, and splenic CD4+ CD25+ regulatory T
cells (Tregs) were examined by flow cytometry. We found that nasal rubbing was
significantly reduced in LFK-fed mice compared to the OVA group on d 27 and 35,
and sneezing was significantly inhibited by LFK administration for 35 d. LFK-fed
mice had significantly less eosinophil influx into the nasal mucosa than the OVA
group. There were no significant differences between the LFK-fed group and OVA
group in the serum and splenocyte culture supernatant levels of IL-4, IFN-γ, and
OVA-specific IgE. Interestingly, the LFK-fed mice had a significantly greater
percentage of splenic CD4+CD25+ Tregs than OVA group. Our results indicate that
oral administration of LFK may alleviate nasal symptoms, reduce nasal eosinophilia,
and increase the percentage of CD4+CD25+ Tregs in experimental allergic rhinitis.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR120311&flag=1
6. X-ray irradiation selectively kills thymocytes of different stages and impairs
the maturation of donor-derived CD4+CD8+ thymocytes in recipient thymus.
J Biomed Res, 2012; 26(5):355-364
Jinbo Lia, Hongquan Caib, Jianliang Jina, Qian Wanga, Dengshun Miaoa
a
The Research Center for Bone and Stem Cells, Department of Human Anatomy,
Nanjing Medical University, Nanjing, Jiangsu 210029, China;
b
Department of Preventive Medicine, School of Public Health, Nanjing Medical
University, Nanjing, Jiangsu 210029, China.
Abstract: The aim of the present study was to determine whether the sensitivity of
thymocytes to X-ray radiation depends on their proliferative states and whether
radiation impairs the maturation of donor-derived thymocytes in recipient thymus. We
assigned 8-week-old C57BL/6J mice into three treatment groups: 1) untreated; 2)
X-ray radiation; 3) X-ray radiation plus bone marrow transplantation with donor bone
marrow cells from transgenic mice expressing enhanced green fluorescent protein
(GFP) on a universal promoter. After 4 weeks, the size of the thymus, the number and
proliferation of thymocytes and ratios of different stage thymocytes were analyzed by
immunohistochemistry and flow cytometry. The results showed that: 1) CD4+CD8+
thymocytes were more sensitive to X-ray radiation-induced cell death than other
thymocytes; 2) the proliferative capacity of CD4+CD8+ thymocytes was higher than
that of other thymocytes; 3) the size of the thymus, the number of thymocytes and
ratios of thymocytes of different stages in irradiated mice recovered to the normal
level of untreated mice by bone marrow transplantation; 4) the ratio of GFP-positive
CD4+CD8+ thymocytes increased significantly, whereas the ratio of GFP-positive
CD4+ or CD8+ thymocytes decreased significantly. These results indicate that the
degree of sensitivity of thymocytes to X-ray radiation depends on their proliferative
states and radiation impairs the maturation of donor-derived CD4+CD8+ thymocytes
in recipient thymus.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?file_no=JBR120507&flag=1
7. Sinomenine reduces iNOS expression via inhibiting the T-bet IFN-γ pathway
in experimental autoimmune encephalomyelitis in rats
Bingjie Gua, Yanying Zengb, Cheng Yina, Huijiuan Wanga, Xiaofan Yanga, Song
Wanga, Xiaohui Jia,*
a
Department of Immunology, Nanjing Medical University, Nanjing, Jiangsu
210029, China;
b
Department of Neurology, the First Affiliated Hospital, Nanjing Medical
University, Nanjing, Jiangsu 210029, China.
Abstract: Sinomenine is a bioactive alkaloid isolated from the Chinese medicinal
plant Sinomenium acutum. It is widely used as an immunosuppressive drug for
treating rheumatic and arthritic diseases. In our previous studies, we found that
sinomenine reduced cellular infiltration within the spinal cord and alleviated
experimental autoimmune encephalomyelitis (EAE) in rats. In this study, we further
investigated the mechanisms of sinomenine treatment in EAE rats. In EAE rats,
treatment with sinomenine exerted an anti-inducible NO synthase (anti-iNOS) effect,
which is related to the reductions of Th1 cytokine interferon-γ (IFN-γ) and its
transcription factor, T-bet, in spinal cords. Moreover, sinomenine treatment of
splenocytes stimulated with anti-CD3 antibody and recombinant rat interleukin 12
reduced the expression of T-bet and IFN-γ in vitro and also reduced the capability of
supernatants of splenocyte culture to induce iNOS expression by primary astrocytes.
However, sinomenine had no direct inhibitory effect on iNOS produced by astrocytes
cultured with IFN-γ and tumor necrosis factor α in vitro. In conclusion, the anti-iNOS
effect of sinomenine on EAE is mediated via the suppression of T-bet /IFN-γ
pathway.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?flag=1&file_no=JBR120608
8. Serum IL-10 from systemic lupus erythematosus patients suppresses the
differentiation and function of monocyte-derived dendritic cells
Zhida Suna, Rong Zhangb, Huijuan Wangc, Pengtao Jiangc, Jiangquan Zhangc,
Mingshun Zhangc, Lei Gud, Xiaofan Yangc, Miaojia Zhangd, Xiaohui Jic*
a
Department of Oral Mucosal Diseases, the Affiliated Stomatological Hospital,
Nanjing Medical University, Nanjing, Jiangsu 210029, China;
b
Laboratory Center for Basic Medical Sciences, Nanjing Medical University,
Nanjing, Jiangsu 210029, China;
c
Department of Microbiology and Immunology, Nanjing Medical University,
Nanjing, Jiangsu 210029, China;
d
Department of Rheumatology, the First Affiliated Hospital, Nanjing Medical
University, Nanjing, Jiangsu 210029, China.
Abstract:The role played by cytokines, other than interferon (IFN)-α, in the
differentiation and function of dendritic cells (DCs) in systemic lupus erythematosus
(SLE), remains unclear. Serum interleukin-10 (IL-10) levels are generally elevated in
SLE patients, which might modulate the differentiation of DCs. In this study, DCs
were induced from monocytes either by transendothelial trafficking or by culture with
granulocyte-macrophage colony-stimulating factor (GM-CSF) + IL-4 + tumor
necrosis factor (TNF)-α. Both systems were used to investigate the effects of elevated
serum IL-10 level on DC differentiation in SLE patients. The results showed that
monocyte-derived DCs induced by either SLE serum or exogenous IL-10 reduced the
expression of human leukocyte antigen (HLA)-DR and CD80, decreased IL-12p40
level, and increased IL-10 level, and exhibited an impaired capacity to stimulate
allogenic T-cell proliferation. These results indicate that serum IL-10 may be involved
in the pathogenesis of SLE by modulating the differentiation and function of DCs.
http://www.jbr-pub.org/ch/reader/view_abstract.aspx?flag=1&file_no=JBR120609