Mannose-binding lectin-associated serine protease 2(MASP-2) is a member of serine protease family and plays a crucial role in activating the complement lectin pathway. When mannose residues on the surface of a pathogen are recognized by mannose-binding lectins (MBL) or fibrinogen collagen (FCN), MASP-2 is activated. This activation then triggers the cleavage of C4 and C2 to form C3 convertase, thereby initiating the lectin pathway of the complement system. Numerous studies have demonstrated that MASP-2 gene polymorphisms and serum levels are closely related with various diseases, including tumors, infectious diseases, autoimmune diseases and so on. In this review, we summarize the relationships between MASP-2 and tumors, infectious diseases, autoimmune diseases. We aim to provide a theoretical basis for the early diagnosis, prognosis evaluation and clinical treatment of various diseases.
Humans ; Mannose-Binding Protein-Associated Serine Proteases/metabolism* ; Neoplasms/metabolism* ; Autoimmune Diseases/genetics* ; Animals ; Polymorphism, Genetic ; Communicable Diseases/genetics*

Two-pore-domain potassium channels (K2P) family is widely expressed in many human cell types and organs, which has important regulatory effect on physiological processes. K2P is sensitive to a variety of chemical and physical stimuli, and they have also been critically implicated in transmission of neural signal, ion homeostasis, cell development and death, and synaptic plasticity. Aberrant expression and dysfunction of K2P channels are involved in a range of diseases, including autoimmune, central nervous system, cardiovascular disease and others. The scope of this review is to give a detailed overview of the structure, function, pharmacological regulation, and related diseases of TREK-1 channels, a member of the K2P family.
Potassium Channels, Tandem Pore Domain/genetics* ; Humans ; Animals ; Cardiovascular Diseases/physiopathology* ; Autoimmune Diseases/metabolism* ; Central Nervous System Diseases/physiopathology*

OBJECTIVE: To explore the role of the CMTM2 gene in regulating testicular spermatogenesis in the mouse model of experimental autoimmune orchitis (EAO). METHODS: We constructed an EAO model in CMTM2 knockout and wild-type (WT) mice, studied the immunological reproductive phenotype and examined the number, morphology and activity of the sperm generated in the CMTM2 knockout mice. We assessed the infiltration of macrophages and lymphocytes in the testis tissue sections and Leydig cells, and determined the expression levels of CMTM2 in the homozygous knockout (KO), heterozygous and WT mice by RT-PCR, Western blot and Northern blot. RESULTS: Statistically significant differences were observed in the long testicular axis and the number of sperm generated between the KO and WT mice after reaching adulthood (P<0.05). The total numbers of macrophages and lymphocytes were markedly increased, while sperm motility and the percentage of morphologically normal sperm remarkably decreased in the testis of the KO mouse model compared with those in the WT mouse model of EAO. CONCLUSION The CMTM2 gene, as a regulator of spermatogenesis, is highly expressed in adult male mice and plays an important role in the maintenance of spermatogenesis. Moreover, decreased expression products of the CMTM2 gene may weaken spermatogenesis under chronic inflammation conditions.
Animals ; Male ; Mice ; Orchitis/genetics* ; Spermatogenesis/genetics* ; Disease Models, Animal ; Testis/metabolism* ; Autoimmune Diseases/genetics* ; Mice, Knockout ; MARVEL Domain-Containing Proteins/genetics*

Vav1, as a key downstream signaling molecule of T cell receptor, includes a catalytic core DH-PH-ZF domain with the function as guanine nucleotide exchange factor (GEF), and a SH3-SH2-SH3 domain with the function as adaptor protein. These two structures of Vav1 play different roles in the development, activation, proliferation and function of T cells, and thereby exert the different regulatory effect on the occurrence and development of autoimmune disease, graft rejection, cancer and other clinical conditions, implicating that Vav1 might be a potential therapeutic target for these diseases. This paper reviews the role of Vav1 in T cells and the occurrence of related diseases.
Adaptor Proteins, Signal Transducing ; Animals ; Autoimmune Diseases ; genetics ; physiopathology ; Humans ; Neoplasms ; genetics ; physiopathology ; Proto-Oncogene Proteins c-vav ; chemistry ; immunology ; metabolism ; T-Lymphocytes

OBJECTIVETo study the effects of Jiawei Huzhang San (JWHZS) decoction on the expressions of the inflammatory factors monocyte chemoattractant protein-1 (MCP-1) and platelet-derived growth factor-BB (PDGF-BB) on experimental autoimmune prostatitis in rats.

METHODSTwelve male Wistar rats were taken as normal controls, and models of experimental autoimmune prostatitis were established in another 60 by injection of SC purified prostate protein with FCA, and then divided into five groups to be treated with normal saline, indomethacin, high-dose JWHZS (0.445 g/kg), medium-dose JWHZS (0.223 g/kg) and low-dose JWHZS (0.089 g/kg), respectively. All the rats were sacrificed at 30 days after the treatment for detection of the mRNA and protein expressions of inflammatory factors by immunohistochemistry and fluorescent quantitative RT-PCR.

RESULTSIn the high-, medium- and low-dose JWHZS groups, the mRNA expressions of MCP-1 (0.31 +/- 0.14, 0.49 +/- 0.21 and 0.62 +/- 0.28) and PDGF-BB (0.50 +/- 0.22, 0.54 +/- 0.17 and 0.71 +/- 0.29), and the protein expressions of MCP-1 (677 +/- 208, 725 +/- 311 and 1302 +/- 884) and PDGF-BB (1265 +/- 698, 1347 +/- 827 and 1655 +/- 812) were significantly lower than in the model control group (MCP-1 mRNA: 1.12 +/- 0.43; MCP-1 protein: 2201 +/- 934; PDGF-BB mRNA: 1.14 +/- 0.51; PDGF-BB protein: 2754 +/- 852) (P < 0.05). And JWHZS exhibited a significantly better activity at high and medium doses than at a low dose (P < 0.05). In the indomethacin control group, both the mRNA and protein expressions of MCP-1 (0.71 +/- 0.34 and 1824 +/- 1157) and PDGF-BB (1.08 +/- 0.37 and 2493 +/- 924) were markedly higher than in the JWHZS groups (P < 0.01).

CONCLUSIONDown-regulation of the inflammatory factors MCP-1 and PDGF-BB may be the important molecular mechanism of JWHZS acting on experimental autoimmune prostatitis.

Animals ; Autoimmune Diseases ; drug therapy ; metabolism ; Chemokine CCL2 ; metabolism ; Disease Models, Animal ; Drugs, Chinese Herbal ; therapeutic use ; Inflammation ; Male ; Phytotherapy ; Platelet-Derived Growth Factor ; metabolism ; Prostatitis ; drug therapy ; metabolism ; Proto-Oncogene Proteins c-sis ; RNA, Messenger ; genetics ; Rats ; Rats, Wistar

To select candidate genes, we attempted to comparative analysis of protein levels between rheumatoid arthritis (RA) patients and healthy controls by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). We identified 17 proteins that showed up- or down-regulated spots in RA patients. We found that coactosin-like1 (COTL1) were highly expressed in RA patients compared with healthy controls. We performed a case-control study to determine whether the COTL1 gene polymorphisms were associated with RA and systemic lupus erythematosus (SLE). The genotype frequency of c.-1124G>T and the allelic frequency of c.484G>A in RA patients, and the genotype frequency of c.484G>A in SLE patients were significantly different from healthy controls (P = 0.009, 0.027, and 0.025, respectively). We also investigated the correlation with the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody in RA patients, and anti-nuclear antibodies (ANA) in SLE patients. The c.484G>A polymorphism in RA patients has significant association with the levels of anti-CCP antibody (P = 0.03). Our findings demonstrated that c.-1124G>T and c.484G>A polymorphisms of the COTL1 gene might be associated with the genetic susceptibility of autoimmune disorders.
Arthritis, Rheumatoid/*genetics/immunology/metabolism ; Autoimmune Diseases/genetics/immunology ; Case-Control Studies ; Electrophoresis, Gel, Two-Dimensional ; Genotype ; Humans ; Lupus Erythematosus, Systemic/genetics/immunology ; Microfilament Proteins/*genetics/metabolism ; Polymorphism, Genetic/*genetics ; Proteome/genetics ; Proteomics/*methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

To select candidate genes, we attempted to comparative analysis of protein levels between rheumatoid arthritis (RA) patients and healthy controls by two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption ionization mass spectrometry (MALDI-TOF-MS). We identified 17 proteins that showed up- or down-regulated spots in RA patients. We found that coactosin-like1 (COTL1) were highly expressed in RA patients compared with healthy controls. We performed a case-control study to determine whether the COTL1 gene polymorphisms were associated with RA and systemic lupus erythematosus (SLE). The genotype frequency of c.-1124G>T and the allelic frequency of c.484G>A in RA patients, and the genotype frequency of c.484G>A in SLE patients were significantly different from healthy controls (P = 0.009, 0.027, and 0.025, respectively). We also investigated the correlation with the levels of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody in RA patients, and anti-nuclear antibodies (ANA) in SLE patients. The c.484G>A polymorphism in RA patients has significant association with the levels of anti-CCP antibody (P = 0.03). Our findings demonstrated that c.-1124G>T and c.484G>A polymorphisms of the COTL1 gene might be associated with the genetic susceptibility of autoimmune disorders.
Arthritis, Rheumatoid/*genetics/immunology/metabolism ; Autoimmune Diseases/genetics/immunology ; Case-Control Studies ; Electrophoresis, Gel, Two-Dimensional ; Genotype ; Humans ; Lupus Erythematosus, Systemic/genetics/immunology ; Microfilament Proteins/*genetics/metabolism ; Polymorphism, Genetic/*genetics ; Proteome/genetics ; Proteomics/*methods ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

T cells recognize antigens through TCRs (T cell receptor). T cell clones can be sorted into 24 gene subfamilies based on the usage of the segments of TCR BV in gene rearrangement. Application of the various segments of TCR BV may establish TCR BV spectrotyping that can be used to analyze and recognize the different functional T cell clones, and understand the function and proliferation of various T cell clones in malignancy and autoimmune disease. In vitro expansion of a great deal of the specific antitumor T cells and transfusing them to patients will be able to develop a new method for tumor immunotherapy. Through analyze the character of the TCR BV gene, McAb against TCR or DNA vaccine to inhibit the growth of T cell clones associated-autoimmune disease and tumors might be developed. The McAb and vaccine may be used to cure these diseases. The commo T cells can also be modifed to specific antitumor T cells by method of TCR gene transfer. In this review, the characteristics of TCR, analysis method for gene spectrotyping of TCR BV, segments of TCR BV and autoimmue distase, T cell clones in hematologic maligrancies, recognition of T cell oligoclone expansion of T cells, and application of TCR BV gene spectrotyping in bone marrow transplantation were discussed and summarised.
Autoimmune Diseases ; genetics ; immunology ; Clone Cells ; cytology ; metabolism ; Gene Rearrangement, beta-Chain T-Cell Antigen Receptor ; genetics ; Hematologic Neoplasms ; genetics ; immunology ; Humans ; Receptors, Antigen, T-Cell ; classification ; genetics ; T-Lymphocyte Subsets ; cytology ; metabolism

OBJECTIVETo investigate the protein and mRNA expression patterns of apoptosis-related genes, together with evidence of apoptosis, in relation to experimental autoimmune inner ear disease (AIED).

METHODSMale C57BL/6 mice at 4 weeks age (n = 80) were randomly assigned to one of the five group (n = 16). The inbred mice were given a single subcutaneous injection of diluted solution of pertussis and an emulsion containing equal parts of complete Freund adjuvant (CFA) and inner ear antigens (IEAg) extracted form guinea pig. The animals were sacrificed for inner ear examination at a defined time after the immunization (7, 14, 21 or 28 days). An autoimmune inner ear diseases model was established. Apoptosis was detected by terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (d-UTP) nick end-laying (TUNEL) method. Using immunohistochemical techniques and reverse transcriptase polymerase chain reaction to clarify the profile of Fas, FasL, and bcl-2.

RESULTSUnder normal conditions, no TUNEL-positive cell was observed in the cochlea except for a few positive cells in the supporting cells of Corti's organ and macula sacculi. Inner ear antigens administration induced TUNEL-positive reactions in a wide variety of cells such as inner hair cells, supporting cells, stria vascularis and spiral ligament fibrocytes. No positive staining was evident in outer hair cells, spiral ganglion cells and Scarpa's ganglion cells during the whole period. Fas proteins were expressed in a wide range of cells in inner ear. The levels of Fas mRNA were no significant differences between normal and AIED mice. FasL and bcl-2 proteins could be detected in spiral ganglion cells and Scarpa's ganglion cells both in normal and AIED mice. FasL positive cells increased in number in inner ear of AIED mice. bcl-2 positive cells were not detectable in inner hair cells, stria vascularis and spiral ligament both in normal and AIED mice. The mRNA of three kinds of apoptosis-related genes was detectable in the normal and AIED mice. FasL mRNA was expressed at low levels in normal, being maximal at 14 d post inoculation and decreased gradually to steady levels by 2 weeks. The levels of bcl-2 mRNA increased significantly during the period of AIED.

CONCLUSIONApoptosis mediated by Fas/FasL signal system may play a role in the initiation and maintenance of AIED. bcl-2 has a crucial role in the regulation of the process of apoptosis in the inner ear of AIED mice.

Animals ; Apoptosis ; Autoimmune Diseases ; genetics ; immunology ; metabolism ; pathology ; Fas Ligand Protein ; genetics ; metabolism ; Guinea Pigs ; In Situ Nick-End Labeling ; Labyrinth Diseases ; genetics ; immunology ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Proto-Oncogene Proteins ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; Spiral Ganglion ; metabolism ; fas Receptor ; genetics ; metabolism

Apoptosis, the cell's intrinsic death program, plays a crucial role in the regulation of tissue homeostasis, and abnormal inhibition of apoptosis is an indicator of cancer and autoimmune diseases, whereas excessive cell death is implicated in neurodegenerative disorders such as Alzheimer's disease (AD). Using cDNA subtraction analysis, we compared p60TRP (p60 transcription regulator protein) expressing cells with control cells during the process of apoptosis and we identified the new zinc-finger protein p48ZnF that is predominantly located in the cytoplasm of the cell. Additionally, we demonstrate here that p48ZnF is up-regulated in rat neuronal PC12 cells upon stimulation with the neurotrophic factor NGF (50 ng/ml). These findings point to a possible pivotal role of p48ZnF in the control of neuronal survival.
Alzheimer Disease/genetics/metabolism ; Animals ; Apoptosis ; Autoimmune Diseases/genetics/metabolism ; Base Sequence ; Biological Markers ; CHO Cells ; Cell Survival/drug effects ; Cloning, Molecular ; Cytoplasm/*metabolism ; DNA-Binding Proteins/*biosynthesis ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Hamsters ; Molecular Sequence Data ; Neoplasms/metabolism ; Nerve Growth Factor/*pharmacology ; Nerve Tissue Proteins/*biosynthesis ; PC12 Cells ; RNA, Messenger/*biosynthesis ; Rats ; Research Support, Non-U.S. Gov't ; Transcription Factors/*biosynthesis/*genetics ; Transfection ; Zinc Fingers/*genetics