Objective To investigate the role of proteasome inhibitor bortezomib (BTZ) in inflammatory response in abdominal aortic aneurysm (AAA) formation induced by angiotensin Ⅱ (Ang Ⅱ). Methods Ang Ⅱ-induced ApoEmice AAA models were established. Forty male ApoEmice (8-10-week-old) were randomly and equally divided into four groups:Sham group,BTZ group,Ang Ⅱ group,and Ang Ⅱ+BTZ group.HE staining,immunohistochemical staining,and flow cytometry were used to analyze the inflammatory response. Real-time quantitative polymerase chain reaction (qPCR) was used to analyze the mRNA expression of intercellular cell adhesion molecule-1 (ICAM-1). Western blotting was used to analyze the activation of nuclear factor κB signaling (NF-κB). Results The mean maximum suprarenal aortic diameter (Dmax) of Sham group,BTZ group,Ang Ⅱ group,and Ang Ⅱ+BTZ group were (1.00±0.01),(0.99±0.01),(1.50±0.13),and (1.20±0.04)mm,respectively (F=8.959,P=0.000). The Dmax of Ang Ⅱ group was significantly larger than those of Sham group (P=0.000) and Ang Ⅱ+BTZ group (P=0.015). The incidence of AAA in Ang Ⅱ group,Ang Ⅱ+BTZ group,and Sham group were 60%,17%,and 0,respectively. HE staining revealed that the abdominal aortic wall thickening was more severe in Ang Ⅱ group than in Sham group and Ang Ⅱ+BTZ group,similar with the infiltration of inflammatory cells. Immunohistochemical staining demonstrated that the CD3T lymphocyte count was significantly higher in Ang Ⅱ group than in Sham group (107.9±15.9 vs. 0,P=0.000) and Ang Ⅱ+BTZ group (107.9±15.9 vs. 0.8±0.5,P=0.000). Flow cytometry also demonstrated that the proportion of the CD3T lymphocytes of the Ang Ⅱ group [(13.50±0.69)%] was significantly higher than that in the Ang Ⅱ+BTZ group [(10.40±0.78)%] at week 1 (t=3.009,P=0.040),and the proportion of the CD3T lymphocytes of the Ang Ⅱ group [(22.70±0.93)%] was significantly higher than that in the Ang Ⅱ+BTZ group [(15.10±0.97)%] at week 4 (t=5.654,P=0.005). The qPCR analysis showed that the mRNA expression of ICAM-1 was significantly up-regulated in Ang Ⅱ group than in Sham group (1.93±0.54 vs. 1.00±0.15,P=0.011) and Ang Ⅱ+BTZ group (1.93±0.54 vs. 0.83±0.08,P=0.009). Western blot analysis showed a lower phosphorylation level of inhibitor of NF-κB in the Ang Ⅱ group compared with the Sham group or Ang Ⅱ+BTZ group,accompanied with an increased phosphorylation level of p65. Conclusion Proteasome inhibitor BTZ can attenuate AAA formation partially by regulating T lymphocytes infiltration through regulating the mRNA expression of ICAM-1 regulated by the activation of NF-κB signaling pathway.
Angiotensin II ; adverse effects ; Animals ; Aortic Aneurysm, Abdominal ; chemically induced ; drug therapy ; Apolipoproteins E ; genetics ; Bortezomib ; pharmacology ; Intercellular Adhesion Molecule-1 ; metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B ; metabolism ; Phosphorylation ; Proteasome Inhibitors ; pharmacology ; Random Allocation ; Signal Transduction ; T-Lymphocytes ; cytology

<b>OBJECTIVEb>To analyze the characteristics of lymphocyte phenotypes in hepatitis B virus (HBV) transgenic mice and the effect of exogenous interferon-α on virological profiles and lymphocytes phenotypes of the mice.

<b>METHODSb>HBV transgenic mice and wild-type (WT) mice were examined for serum levels of HBsAg, HBcAb, IL-21, and IL-6 using ELISA. The frequencies of CD4(+)T and CD19(+)B cells separated from the liver, spleen, and peripheral blood were detected by flow cytometry. Nine HBV transgenic mice were injected subcutaneously with recombinant mouse interferon alpha (rmIFN-α) and another 9 transgenic mice were injected with PBS, and their HBsAg, HBV DNA, IL-6, and IL-21 levels and frequencies of peripheral blood CD4(+)T and CD19(+)B cells were detected.

<b>RESULTSb>HBV transgenic mice showed a high level of HBsAg with a detectable level of HBcAb and significantly increased serum levels of IL-21 and IL-6 as compared with WT mice (P<0.05). The transgenic mice had a significantly lower frequency of CD4(+) T cells in the peripheral blood, liver and spleen (P<0.05) but a significantly higher frequency of CD19(+) B cells in the liver (P<0.05). An inverse correlation between intrahepatic CD4(+) T cell frequency and serum HBsAg level while a positive correlation between intrahepatic CD19(+) B cell frequency and HBcAb level were found in HBV transgenic mice. Administration of rmIFN-α significantly increased the frequencies of CD4(+) T and CD19(+) B cells in the peripheral blood and the serum level of IL-6 in HBV transgenic mice (P<0.05).

<b>CONCLUSIONb>HBV transgenic mice have lymphocyte subset dysregulation and exogenous interferon-α can modulate the immune function of the mice by regulating the frequencies of lymphocyte subsets.

Animals ; Antiviral Agents ; pharmacology ; B-Lymphocytes ; drug effects ; DNA, Viral ; blood ; Hepatitis B ; drug therapy ; immunology ; Hepatitis B Antibodies ; blood ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; Interferon-alpha ; pharmacology ; Interleukin-6 ; blood ; Interleukins ; blood ; Liver ; immunology ; Lymphocyte Subsets ; cytology ; drug effects ; Mice ; Mice, Transgenic ; Phenotype ; T-Lymphocytes ; drug effects

<b>OBJECTIVEb>To investigate the effects of inhibiting TIM-4 function in Kupffer cells (KCs) on liver graft rejection in mice and explore the underlying mechanism.

<b>METHODSb>Mouse models of orthotopic liver transplantation were treated with a control mAb group and TIM-4 mAb. The activated KCs were assayed with immunohistochemistry after operation. The expression of TIM-4 in KCs were assayed with Western blotting and RT-PCR and the levels of AST, ALT, TBIL, TNF-α, IFN-γ and CCL2 were assayed detected. The expression of TIM-4 in KCs was observed with laser confocal microscopy. HE staining was used to observe the microstructure of the liver tissues, and the number of CD25Foxp3T cells was determined using with flow cytometry; the proteins levels of p-P65and p-P38 were assayed with Western blotting. The donor mice were treated with clodronate liposomes to destroy the KCs in the liver before transplantation, and the liver grafts were examined for graft rejection.

<b>RESULTSb>The number of activated KCs in the liver graft increased progressively over time. Compared with the sham-operated group, the liver graft showed significantly increased TIM-4 protein and mRNA levels at 1, 3, and 7 days after transplantation (P<0.05) and increased levels of AST, ALT, TBIL, TNF-α, IFN-γ and CCL2 at 7 days (P<0.05). The graft in TIM-4 mAb group showed mild pathological changes with a mean RAI score of 2.67∓0.75, which was significantly lower than that in control mAb group (P<0.05). The mean survival time of the recipient mice was 53.8∓6.4 days in TIM-4 mAb group, significantly longer than that in the control mAB group (14.5∓2.9 days, P<0.05). Donor treatment with clodronate liposomes resulted in comparable RAI scores in TIM-4 mAb and control mAb groups (8.01∓0.64 vs 7.93∓0.56, P>0.05). The protein levels of p-P65 and p-P38 in TIM-4 mAb group were significantly lower than those in control mAb group (P<0.05), and CD25Foxp3T cells in the liver graft increased significantly in TIM-4 mAb group.

<b>CONCLUSIONb>Inhibition of TIM-4 function in KCs reduces the production of inflammatory factors after liver transplantation possibly by inhibiting the NF-κB and MAPK signaling pathways and promoting the proliferation of Foxp3Treg cells to induce allograft tolerance.

Animals ; Antibodies, Monoclonal ; pharmacology ; Graft Rejection ; Immunohistochemistry ; Kupffer Cells ; drug effects ; metabolism ; Liver ; surgery ; Liver Transplantation ; Male ; Membrane Proteins ; antagonists & inhibitors ; Mice ; NF-kappa B ; metabolism ; T-Lymphocytes, Regulatory ; immunology

Chronic prostatitis is a common male disease, and its pathogenesis is not yet clear. Most scholars believe that oxidative stress and immune imbalance are the keys to the occurrence and progression of chronic prostatitis. Currently immunotherapy of chronic prostatitis remains in the exploratory stage. This article relates the active ingredients of 5 Chinese medicinal herbs (total glucosides of paeony, tripterigium wilfordii polglycosidium, curcumin, geniposide, and quercetin) for the treatment of chronic prostatitis and their possible action mechanisms as follows: 1) inhibiting the immune response and activation and proliferation of T-cells, and adjusting the proportion of Th1/Th2 cells; 2) upregulating the expression of Treg and enhancing the patient's tolerability; 3) suppressing the activation of the NF-kB factor, reducing the release of iNOS, and further decreasing the release of NO, IL-2 and other inflammatory cytokines, which contribute to the suppression of the immune response; 4) inhibiting the production of such chemokines as MCP-1 and MIP-1α in order to reduce their induction of inflammatory response. Studies on the immune mechanisms of Chinese medicinal herbs in the treatment of chronic prostatitis are clinically valuable for the development of new drugs for this disease.
Chemokines ; immunology ; Cytokines ; immunology ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Immune System ; drug effects ; Male ; NF-kappa B p50 Subunit ; metabolism ; Nitric Oxide Synthase Type II ; metabolism ; Plants, Medicinal ; Prostatitis ; drug therapy ; immunology ; T-Lymphocytes, Regulatory ; drug effects ; Th1-Th2 Balance

<b>BACKGROUNDb>The prevalence of hepatitis B virus (HBV) infection is high among individuals infected with human immunodeficiency virus (HIV) in China. Both HIV and HBV can be treated with tenofovir disoproxil fumarate (TDF) and lamivudine (3TC), so we evaluated the safety and efficacy of combination antiretroviral therapy (ART) that included TDF, 3TC, and efavirenz (EFV) among ART-naive individuals who were co-infected with HIV and HBV.

<b>METHODSb>One hundred HIV/HBV co-infected ARV-naive individuals were started on the regimen of TDF, 3TC, and EFV, and the levels of plasma HBV DNA, HIV RNA, and biochemical evaluation related to the function of liver and kidney were analyzed.

<b>RESULTSb>Concerning efficacy, this study found that by week 48, the vast majority co-infected participants receiving this ART regimen had undetectable HBV DNA levels (71%) and/or HIV RNA levels (90%). Concerning safety, this study found that the median estimated glomerular filtration rate of participants decreased from baseline (109 ml·min-1·1.73 m-2) to week 12 (104 ml·min-1·1.73 m-2) but was almost back to baseline at week 48 (111 ml·min-1·1.73 m-2).

<b>CONCLUSIONb>This combination ART regimen is safe and effective for patients with HIV/HBV co-infection.

<b>TRIAL REGISTRATIONb>ClinicalTrials.gov, NCT01751555; https://clinicaltrials.gov/ct2/show/NCT01751555.

Adult ; Alanine Transaminase ; metabolism ; Anti-HIV Agents ; therapeutic use ; Aspartate Aminotransferases ; metabolism ; Benzoxazines ; therapeutic use ; CD4-Positive T-Lymphocytes ; metabolism ; Coinfection ; drug therapy ; Female ; HIV Infections ; drug therapy ; Hepatitis B virus ; drug effects ; pathogenicity ; Humans ; Lamivudine ; therapeutic use ; Male ; Tenofovir ; therapeutic use

BACKGROUND/AIMS: Inflammatory bowel disease (IBD) is a chronic disease of the gastrointestinal tract, whose etiologies are still unknown. This study was performed to evaluate the humoral immune response in terms of B cell functions in selected IBD patients. METHODS: Eighteen pediatric patients with IBD, including 12 cases of ulcerative colitis (UC) and six with Crohn disease (CD), were enrolled in this study. The pneumococcal vaccine was injected in all patients, and the IgG antibody level to the polysaccharide antigen was measured before and 4 weeks after injection. The B cell switch-recombination process was evaluated. RESULTS: Five patients with IBD (three CD and two UC) had defects in B cell switching, which was significantly higher than in controls (p=0.05). Ten patients had a specific antibody deficiency and exhibited a higher frequency of bacterial infection than the healthy group. The mean increased level of IgG after vaccination was lower in IBD patients (82.9+/-32.5 microg/mL vs 219.8+/-59.0 microg/mL; p=0.001). Among the patients who had an insufficient response, no significant difference in the number of switched memory B-cell was observed. CONCLUSIONS: A defect in B lymphocyte switching was observed in pediatric IBD patients, and especially in those patients with CD. Owing to an increased risk of bacterial infections in those patients with antibody production defects, pneumococcal vaccination could be recommended. However, not all patients can benefit from the vaccination, and several may require other prophylactic methods.
Adolescent ; Antibody Formation/*drug effects ; B-Lymphocytes/metabolism ; Child ; Child, Preschool ; Colitis, Ulcerative/complications/*immunology ; Crohn Disease/complications/*immunology ; Female ; Humans ; Immunoglobulin G/metabolism ; Inflammatory Bowel Diseases/complications/*immunology ; Male ; Pneumococcal Vaccines/*pharmacology ; Polysaccharides/*pharmacology ; Treatment Outcome

<b>OBJECTIVEb>To investigate the effects of rituximab (RTX) in children with steroid-dependent nephrotic syndrome.

<b>METHODb>Five cases of children with steroid-dependent nephrotic syndrome seen from May 2012 to February 2013 in whom only steroid plus calcineurin inhibitor was effective and the disease recurred on reduction of dose were enrolled into this study, including 3 males and 2 females. Calcineurin inhibitors were stopped and steroids was changed to full dose. After the general condition improved, RTX was given at a dose of 375 mg/m(2), once a week for a total of three times for one course. After urine protein became negative for five days, the dose of steroid was changed to 2 mg/kg every other day, thereafter the dose was reduced by 5 mg per every 2 weeks, until discontinuation. After regular monitoring, when peripheral blood B cells were ≥ 3%, a second RTX was added.

<b>RESULTb>Urine protein was negative in 2-7 days in 5 patients after the first RTX treatment. Before treatment B lymphocytes in peripheral blood was 7.8% to 13.0% and after the first course of RTX treatment decreased to 0 in the first 6 to 8 months at the beginning of recovery, while in the first 7 to 10 months to 3.3%-6.1%, after a second RTX was given, B lymphocytes were reduced to 0, but in two cases (cases 1 and 3) B lymphocytes rose again at 16 and 17 months, in the first 17 and 18 months rose to 4.16% and 4.17%, RTX was given once again respectively. B lymphocytes were reduced to 0 again. Currently the 5 patients continued to be negative for urine protein, maintaining remission for 12 to 20 months.RTX infusion had no significant side effects, and side effects of steroid and calcineurin inhibitor disappeared.

<b>CONCLUSIONb>In children with steroid-dependent and only calcineurin inhibitor effective nephritic syndrome, relapse may still occur after improvement of nephrotic syndrome, after the first RTX treatment, regular monitoring of B lymphocytes, RTX supplementary treatment in advance can help discontinuation of steroids and immunosuppressive agents and maintain remission.

Anti-Inflammatory Agents ; administration & dosage ; therapeutic use ; Antibodies, Monoclonal, Murine-Derived ; administration & dosage ; therapeutic use ; Antigens, CD19 ; metabolism ; B-Lymphocytes ; drug effects ; metabolism ; Calcineurin Inhibitors ; administration & dosage ; therapeutic use ; Child ; Child, Preschool ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Immunosuppressive Agents ; administration & dosage ; therapeutic use ; Lymphocyte Count ; Male ; Nephrotic Syndrome ; drug therapy ; metabolism ; Proteinuria ; urine ; Recurrence ; Remission Induction ; Rituximab ; Treatment Outcome

<b>OBJECTIVEb>To explore the improvement of dendritic cells' (DCs) functions in chronic hepatitis B (CHB) patients by two different drugs plasma, i.e., Shen supplementing and detoxification (SSD) and Pi invigorating and detoxification (PID), thus comparing which method was more effective to activate DCs to improve T lymphocyte functions.

<b>METHODSb>Totally 30 CHB outpatients were recruited. They were assigned to the immune tolerant group and the immune clearance group, 15 in each group. Totally 60 mL peripheral blood was extracted to isolate and develop mature DCs. Chinese compound containing (Liuwei Ganlu Syrup for SSD) and (Sijun Ganlu Syrup for PID) plasma were added to promote the maturation of DCs on the 7th day. Besides, non-drug plasma was taken as the control. On the ninth day, HBV core 18-27 loaded core peptide and its own T lymphocyte were co-cultivated for 72 h. Then T lymphocytes were collected. The expression levels of CD3, CD28, CD4, and CD8, programmed death-1 (PD-1) were detected using flow cytometry.

<b>RESULTSb>Compared with non-drug plasma, the expression levels of CD3, CD4, and CD28 could be improved, and the expression levels of CD8 and PD-1 could be reduced by the two methods, showing statistical difference (P < 0.05). Besides, SSD containing plasma showed better effect in improving the molecular CD28 expression rate, and reducing the molecular PD-1 expression rate on the T cell surface, showing statistical difference when compared with that of PID containing plasma (P < 0.05).

<b>CONCLUSIONSb>In vitro intervention of DCs by SSD and PID containing plasmas combined co-cultivation of its own T lymphocytes could promote the activation of DCs to improve the function of T cells and the expression of T cell surface molecules. Besides, SSD showed more significant effect on infection immune of HBV patients in the tolerance stage.

Adult ; Cells, Cultured ; Dendritic Cells ; drug effects ; immunology ; Drugs, Chinese Herbal ; pharmacology ; Female ; Hepatitis B, Chronic ; immunology ; Humans ; Male ; Middle Aged ; T-Lymphocytes ; immunology ; Young Adult

<b>OBJECTIVEb>To explore the effect of compound qizhu granule (CQG) on cellular immunity of chronic hepatitis B (CHB) patients.

<b>METHODSb>Totally 103 CHB patients treated with lamivudin (LAM) for 6 months, who had partial virological response (HBeAg positive) were randomly assigned to two groups, 50 in the treatment group and 53 in the control group. All patients took LAM 100 mg (once a day) plus ADV 10 mg (once a day). Patients in the treatment group additionally took CQG, one dose per day. After one-year treatment hepatitis B virus (HBV) DNA negative rates, HBeAg seroconversion, levels of HBV specific cytotoxic T lymphocyte (CTL), non-specific CTL and natural killing (NK) cells were compared between the two groups.

<b>RESULTSb>After 1-year treatment, HBV DNA negative rate of the treatment group was 88: 0% in 44 cases, slightly higher than that of the control group (41 cases, 77.4%), but with no statistical difference (P >0.05). HBeAg seroconversion of the treatment group was 32.0% in 16 cases, higher than that of the control group (8 cases, 15.1%), with statistical difference (P <0.05). Levels of HBV specific CTL (0.79%±0. 07%), non-specific CTL (19.4%±1.8%) and NK cells (14. 1%± 1.5%) of the treatment group were higher than those of the control group (0.58% ± 0.08%, 17.5% ± 1.7%, and 11.1%±1.5%, respectively; allP <0.01).

<b>CONCLUSIONb>Treating CHB patients with partial virological response by ADV plus CQG could improve specific and non-specific cellular immunity, thereby elevating HBeAg seroconversion rate.

Drugs, Chinese Herbal ; therapeutic use ; Hepatitis B e Antigens ; immunology ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; drug therapy ; immunology ; Humans ; Immunity, Cellular ; immunology ; T-Lymphocytes, Cytotoxic ; drug effects

AIM: Radiation induces an important apoptosis response in irradiated organs. The objective of this study was to investigate the radioprotective effect of tetramethylpyrazine (TMP) on irradiated lymphocytes and discover the possible mechanism of protection. METHOD: Lymphocytes were pretreated for 12 h with TMP (25-200 μmol·L(-1)) and then exposed to 4 Gy radiation. Cell apoptosis and the signaling pathway were analyzed. RESULTS: Irradiation increased cell death, DNA fragmentation, activated caspase activation and cytochrome c translocation, downregulated B-cell lymphoma 2 (Bcl-2) and up-regulated Bcl-2-associated X protein (Bax). Pretreated with TMP significantly reversed this tendency. Several anti-apoptotic characteristics of TMP, including the ability to increase cell viability, inhibit caspase-9 activation, and upregulate Bcl-2 and down-regulate Bax in 4Gy-irradiated lymphocytes were determined. Signal pathway analysis showed TMP could translate nuclear factor-κB (NF-κB) from cytosol into the nucleus. CONCLUSION The results suggest that TMP had a radioprotective effect through the NF-κB pathway to inhibit apoptosis, and it may be an effective candidate for treating radiation diseases associated with cell apoptosis.
Apoptosis ; drug effects ; radiation effects ; Cell Line ; Cell Survival ; drug effects ; radiation effects ; DNA Fragmentation ; drug effects ; radiation effects ; Drugs, Chinese Herbal ; pharmacology ; Humans ; Lymphocytes ; cytology ; drug effects ; radiation effects ; NF-kappa B ; genetics ; metabolism ; Proto-Oncogene Proteins c-bcl-2 ; genetics ; metabolism ; Pyrazines ; pharmacology ; Radiation-Protective Agents ; pharmacology ; bcl-2-Associated X Protein ; genetics ; metabolism