ABSTRACT
Diffuse large B-cell lymphoma (DLBCL) is the most common malignant lymphoma in China,which mostly starting from the lymph nodes.The studies find that the expression of NLRC5,member of nucleotide-binding oligomerization domain-like receptor (NLR) family,is evident in the lymphoid cells,which is likely to be an important basis for lymphocyte tumorigenesis.NLRC5 can block the nuclear factor-κB (NF-κB),a core component of signal transduction pathway,and affect the development of tumor.While continuing activation of NF-κB is a necessary condition for DLBCL cell survival.Therefore,NLRC5 is likely to inhibit excessive inflammation,thereby inhibiting the function of DLBCL,which promises to be a new target for immunotherapy treatment of DLBCL.
ABSTRACT
Objective To explore the effect of MICA-Ab expression on the prognosis of sensitized renal transplantation recipients.Methods A total of 51 sensitized recipients (PRA more than 20%) in our hospital from August 2007 to April 2010 were enrolled in the study.In these patients,29 cases received protein A immunoadsorption and detection of MICA-Ab was performed before and after protein A immunoadsorption.Other 22 patients received MICA-Ab detection when they were hospitalized.Associations of PRA,HLA-matches,acute rejection,and serum creatinine of postoperative week 1 and week 4 with MICA-Ab were analyzed retrospectively.Results Sixteen recipients (31.4%) had positive MICA-Ab expression but their acute rejection rate was not higher as compared to the patients with negative MICA-Ab expression.Recipients with PRA＞40% showed higher expression level of MICA-Ab than recipients with PRA≤40% (P≤0.05).HLA-match did not show influence on MICA-Ab expression.MICA-Ab positive group had no higher serum creatinine level than negative group in postoperative week 4.MICA-Ab level decreased significantly after protein A immunoadsorption.Conclusions MICA-Ab expression increases in the sensitive recipients but does not influence the prognosis.Protein Aimmunoadsorption can eliminate MICA-Ab effectively in sensitized recipients.
ABSTRACT
Objective To investigate the function of major histocompatibility complex (MHC)class Ⅰ-related gene (MIC) in ulcerative colitis (UC) pathogenesis. Methods The difference of MICA, M ICB and their ligand NKG2D genes expression in colonic mucosa tissue of 34 UC patients and 12 healthy people were determined by fluorescent real-time reverse-transcriptase polymerase chain reaction (RT-PCR) and the expression location of M ICA in colonic mucosa tissue was obtained by laser scanning confocal microscope. Results The mRNA level of MICA, MICB and NKG2D expression in UC groups (3. 5408±2. 6658, 8. 9879±3. 2893 and 2. 4395±0. 8147 accordingly) was significantly higher than that in the healthy controls ( 1. 0477 ± 0. 7201, 4. 6293 ± 1. 2616 and 1. 1624±0. 3954 accordingly) (P = 0.0053, 0.0039 and 0. 0078 accordingly). It suggested that MICA was expressed in colonic epithelia cell membranes by laser scanning confocal microscopy.Conclusion The mRNA level of MICA, M ICB, and their ligand, NKG2D expression were all up regulated in the colonic mucosa of UC patients, which indicated MIC gene might perform important local function in UC.
ABSTRACT
Objective To investigate the prediction of anti-human leukocyte antigen antibodies (HLA) and anti-major histocompatibility complex class I-related chain A antibodies (MICA) to the development of acute rejection (AR) and kidney allograft function. Methods Forty-one kidney transplant patients were prospectively tested for anti-HLA and anti-MICA. Thirty-seven patients were screened using Luminex/single-antigen beads to determine the HLA and MICA-specific antibody levels at 0,30,90, 180,360,720 and 1080 days post-transplantation. The patients and donors of HLA and MICA allele typing were determined by PCR-SSOP, and donor specific antibody (DSA) and non-donor specific antibody (NDSA) were identified.Simultaneously,their serum creatinine (SCr) levels and clinical data were analyzed. Results Nine patients (21.95 % ,9/41 ) had pre-existing anti-HLA and(or) anti-MICA, including 6 cases of anti-MICA,2 cases of anti-HLA, and one case of anti-MICA and anti-HLA. Nine patients had pre-existing DSA and NDSA. In the 37 patients, 6 patients (16.2% ) developed de novo anti-HLA, and 3 (8.1%) developed de novo antiMICA. In patients positive for de novo anti-HLA, the titer of antibody was gradually increased during the follow-up of three years. Four patients out of 9 patients with pre-existing antibodies were suffered from AR (44.4%); In 6 patients positive for de novo anti-HLA,three cases (50.0%) were suffered from AR; In three patients positive for de novo anti-MICA,no AR occurred (P＜0.05). In two patients positive for DSA of HLAⅡ antibody detected at the third and seventh day after transplantation, the renal grafts were renovecd due to rejection. The Scr levels in patients positive for pre-existing MICA with AR were higher than in those positive for pre-existing MICA without AR at each scheduled time point during the follow-up period (P＜0.05). The Scr levels in patients negative for antibodies pre-transplantation and having AR were higher than in those having no AR at each scheduled time point during the follow-up period (P＜0. 01 ). The Scr levels in patients positive for de novo HLA and MICA and having AR one month following transplantation were higher than in those negative for antibodies and having no AR (P＜0.01 ). Conclusion Pre-existing and de novo anti-HLA were the irnportant factors for the development of AR, but the mismatch of HLA and MICA alleles in donors and patients was primary causes for generation of de novo antibodies.
ABSTRACT
Objective To observe the expression of cytotoxicity and receptors on NK cells in breast cancer,and investigate the impact of soluble MICA(sohble MHC class Ⅰ-related molecules A,sMICA) on NK cells receptors expression and cytotoxicity.Methods ELISA was used to examine the sMICA in peripheral blood.The expressions of activated receptor(NKG2D),killer inhibitory receptor (KIR)(CD158b) and NK cells were identified by flow cytometry(FCM).Cytotoxicity of NK cells to breast cancer were tested by MTT.Results sMICA was (205.36±71.27)ng/L in breast cancer patients and 81.6 % samples were detected.There were positive correlations between sMICA levels with breast cancer stages.There were no difference of NK cells percentage between breast cancer and healthy person.The cytotoxicity of NK cells and expressions of NKG2D were obviously lower in breast cancer with sMICA(+) than in healthy person,but CD158b was higher in healthy person.After cultured with sMICA,NK cells cytotoxicity decreased from(76.2±6.7)% to(48.4±4.1)% and the expression of NKG2D reduced from(92.5±7.1)% to (62.5±6.4)%,but the the expression of CD158b increased from(10.6±3.2)% to (43.6±3.4)%.IL-15 up regulated the expression of NKG2D and NK cells cytotoxicity,but decreased the expression of CD158b by co-culturation with IL-15 and sMICA in sMICA+ patients with breast cancer.Conclusion sMICA reduced the expression of NKG2D and increased the expression of Kill,which lead to the down regulation of NK cells cytotoxicity.IL-15 can reverse this effect.
ABSTRACT
Objective To observe the regulatory effect of recombinant human DCN on the expression of HLA class Ⅰ, Ⅱ molecule on hepatoma carcinoma cell HepG2 and investigate the relatively immune mechanism of human DCN on enhancing anti-tumor effect. Methods After transfected HepG2 cells with pcDNA3.1 (+)-DCN by liposome transfection, the expression of HLA class Ⅰ , Ⅱ molecule and the apoptotic indexes were analyzed by the flow cytometer. Results The expression of HLA class Ⅰ , Ⅱ molecule on the HepG2 cells transfected with pcDNA3.1 (+)-DCN was up-regulated with the apoptosis indexes being significantly higher than that of other control groups. Conclusion The human DCN can induce HepG2 apoptosis and up-regulate the expressions of HLA class Ⅰ , Ⅱ molecule which may contribute to its antitumor effect.
ABSTRACT
Objective To explore the expression of transporter associated with antigen processing (TAP) and major histocompatibility complex class (MHC)-Ⅰ molecule in malignant melanoma cell lines. Methods Three malignant melanoma cell lines, including A375, A875, and KZ28 cells as well as normal melanocytes were cultured. Western blot, reverse transcription PCR and flow cytometry were used to detect the protein and mRNA expression of TAP as well as the membrane expression of MHC-Ⅰ in these cells. Results A significant decrease was observed in the expression of TAP mRNA (t = 5.89, 4.45 and 4.57 re-spectively, all P< 0.01) and protein (t= 5.46, 4.32 and 4.67 respectively, all P< 0.01) in A375, A875 and KZ28 cells compared with the melanocytes, with the strongest decrease occurring in A375 cells. Similarly, the expression of MHC-Ⅰ molecule was significantly lower in A375, A875 and KZ28 cells than that in the melanocytes (t= 6.16, 5.22 and 5.61 respectively, all P< 0.01).Conclusions The protein and mRNA expres-sion of TAP is down-regulated in three melanoma cell lines A375, A875 and AZ28, which may contribute to the escape of melanoma cells from human immune surveillance.
ABSTRACT
Objectives To study the clinical diagnostic value of soluble major histocompatibility complex class Ⅰ-related chain A(sMICA) and analyse the relationship of tumor biologic characteristics and sMICA in lung cancer. Methods The experimental level of sMICA was determined by ELISA in 116 lung cancer patients. The level of serum CEA, NSE, CA-199, CYFRA-211, SCC, ProGRP were determined by ELISA only in 91 lung cancer patients without any therapy. The level of sMICA in 50 normal persons was regarded as control group. Results The level of sMICA in lung cancer patients was significantly higher than that in control group (P<0.001); When sMICA cut-off was set as 240.5 ng/L, the sensitivity for the detection of lung cancer was 90.1%, the speciality was 46.9%. The positive rate of sMICA was significantly higher than that of CEA, NSE, CA-199, CYFRA-211, SCC, ProGRP(P<0.001 respectively); The level of sMICA in lung cancer patients with CR and PR after treatment were lower than that before treatment(P<0.05). The level of sMICA in lung cancer patients with relapse was higher than patients without any treatment (P<0.001). Conclusion SMICA may be a potential marker for diagnosing lung cancer with high sensitivity and speciality. It is associated with tumor progression and distant metastasis and may be helpful in the evaluation of diagnosis for lung cancer.
ABSTRACT
AIM: The expression of the mouse ? 2 microglobulin (? 2 m) in NIH3T3 cells transfected with the mouse ? 2m sense and antisense RNA was detected to clarify the effect of mouse ? 2m sense and antisense RNA on the expression of MHC classⅠgene. METHODS: The mouse sense and antisense RNA, pcDNA3-? 2mSN and pcDNA3-? 2mAN, were constructed and were transfected into NIH3T3 cells by lipofectamine. RT-PCR and Western blot were used to detect the expression of ? 2m in those cells. RESULTS: The expression of the mouse ? 2m in the cells transfected with pcDNA3-? 2mSN was increased, while it was decreased in those cells transfected with pcDNA3-? 2mAN. CONCLUSION: pcDNA3 -? 2mAN can downregulate the expression of the ? 2m in NIH3T3 cells.