Kinetin (Kn) is a cytokinin growth factor that exerts several anti-aging and antioxidant effects on cells and organs. To investigate the mechanism underlying apoptotic events in aging cells induced by D-galactose (D-gal), we examined the effect of Kn delivered via nuchal subcutaneous injection on D-gal-induced aging and apoptosis in rats. Our results showed that interleukin (IL)-2 levels and mitochondrial membrane potential (DeltaPsim) were decreased by Kn in aging rats while IL-6 production and apoptosis increased. In addition, the expression of anti-apoptotic Bcl-2 was low while that of Bax was high in the aging group. After treated with Kn, compared with aging group, there showed obvious difference in Kn group with elevated IL-2, proliferation index, Bcl-2, DeltaPsim and decreased IL-6 and Bax in splenic lymphocyte. Based on these results, we concluded that Kn can effectively protect the rat spleen from aging, apoptosis, and atrophy.
Aging/drug effects/physiology ; Animals ; Apoptosis/drug effects/*physiology ; Female ; Galactose/*pharmacology ; Interleukin-6/physiology ; Interleukins/physiology ; Kinetin/pharmacology/*physiology ; Male ; Membrane Potential, Mitochondrial/drug effects/physiology ; Rats ; Spleen/*cytology/drug effects/physiology

OBJECTIVEThis study aimed to detect the immunoexpression of interleukin-21 (IL-21) and receptor activator. of nuclear factor KB ligand (RANKL) in periapical granulomas (PGs) and radicular cysts (RCs). The interaction of IL-21 with RANKL and its role in periapical pathogenesis were also speculated.

METHODSA total of 32 PGs and 23 RCs were selected as experimental samples. Lesion size and occurrence of tenderness were recorded. Up to 10 healthy gingival tissues were collected as normal control samples. All tissues were subjected to immunohistocheincal analysis with anti-human IL-21 and RANKL polyclonal antibodies. The correlations of IL-21 with RANKL, lesion size, and the occurrence of tenderness of the PGs and RCs were evaluated.

RESULTSIL-21-positive cells were detected in all periapical lesion tissues but not in normal tissues. In the cyst group and granuloma group, the corresponding expression levels of IL-21 were 59.92±6.57 and 36.80± 6.81, whereas those of RANKL were 68.81±18.59 and 36.12±14.87, respectively. Moreover, t-test revealed a significantly higher expression of IL-21 and RANKL in RCs than in PGs (P<0.05). IL-21 and RANKL were positively correlated in both PGs and RCs (P<0.05). Furthermore, IL-21 was correlated with lesion size (P<0.05).

CONCLUSIONThis study demonstrated that IL-21 is potentially involved in the pathogenesis of apical periodontitis lesions. A role in the exacerbation of chronic inflammation, as well as in bone resorption, is suspected. Further studies are required to elucidate the specific functions of IL-21 in periradicular inflammatory processes.

Humans ; Inflammation ; Interleukins ; physiology ; NF-kappa B ; metabolism ; Periapical Granuloma ; metabolism ; Periapical Periodontitis ; RANK Ligand ; Radicular Cyst ; metabolism

BACKGROUND/AIMS: Gastric juice plays a crucial role in the physiology of the stomach. The aim of this study is to evaluate associations among the pH of gastric juice, atrophic gastritis (AG), intestinal metaplasia (IM), pepsinogen, and Helicobacter pylori infection. METHODS: Gastric biopsies and juice were collected from 46 subjects who underwent endoscopies at Seoul National University Bundang Hospital between November 2011 and March 2013. H. pylori, AG and IM were evaluated, and pepsinogen I or II, I/II ratio, and interleukin (IL)-1β levels were measured. RESULTS: The mean pH of gastric juice was higher in the H. pylori-positive group (n=17) than that in the H. pylori-negative group (n=29) (4.54 vs 2.46, p=0.002). When patients were divided into pH < 3 (n=28) and pH ≥3 (n=18) groups, H. pylori was lower in the pH < 3 group (21.4%) than in the pH ≥3 group (61.1%) (p=0.007). The pH ≥3 group demonstrated AG and IM more frequently than the pH < 3 group in the body (p=0.047 and p=0.051, respectively) but not in the antrum. There were no differences in pepsinogen I or II, I/II ratio, and IL-1β levels between the two groups. CONCLUSIONS: There is a relationship between chronic H. pylori infection and gastric juice pH ≥3, which may originate from AG and IM in the body.
Biopsy ; Gastric Juice* ; Gastritis ; Gastritis, Atrophic* ; Helicobacter pylori* ; Helicobacter* ; Humans ; Hydrogen-Ion Concentration* ; Interleukins ; Metaplasia* ; Pepsinogen A ; Physiology ; Seoul ; Stomach

OBJECTIVETo study the roles of CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) and IL-33 in the pathogenesis of asthma in children.

METHODSFlow cytometry was used to detect peripheral blood CD4(+)CD25(+)Foxp3(+)Treg proportion in CD4(+)T lymphocytes in.45 children with asthma, 50 children with wheezing caused by respiratory syncytial virus infection and 40 healthy children. Serum levels of IFN-γ, IL-4, IL-5 and IL-33 were measured using ELISA.

RESULTSThe level of peripheral blood CD4(+)CD25(+)Foxp3(+)Treg in the asthma group was significantly lower than in the wheezing and control groups (P<0.05). In contrast, serum levels of IL-33 in the asthma group was significantly higher than in the wheezing and control groups (P<0.05). Peripheral blood CD4(+)CD25(+)Foxp3(+)Treg level was negatively correlated with serum IL-33 level in the asthma group(r=-0.156, P<0.01).

CONCLUSIONSCD4(+)CD25(+)Foxp3(+)Treg may interact with IL-33 in the pathogenesis of childhood asthma.

Asthma ; etiology ; immunology ; Child ; Child, Preschool ; Female ; Forkhead Transcription Factors ; analysis ; Humans ; Infant ; Interleukin-2 Receptor alpha Subunit ; immunology ; Interleukin-33 ; Interleukins ; physiology ; Male ; T-Lymphocytes, Regulatory ; physiology

Interleukin-21 (IL-21) is a new member of the interleukin-2 family. It is mainly synthesized and secreted by the activated of CD4(+) T cells and natural killer T cells. IL-21 receptor (IL-21R) is mainly expressed in T cells, B cells, and natural killer (NK) cells. After binding to its receptor, IL-21 can regulate the activation and proliferation of T cells, B cells, and NK cells through activating JAKs-STATs signaling pathways. As a new immunoregulatory factor, IL-21 and its receptor play important roles in the development and progression of various autoimmune diseases. Regulation of the expression levels of IL-21 and IL-21R and blocking of their signal transduction pathways with blockers may be new treatment options for autoimmune diseases.
Animals ; Autoimmune Diseases ; etiology ; immunology ; Dendritic Cells ; immunology ; Humans ; Interleukins ; physiology ; Killer Cells, Natural ; immunology ; Lymphocytes ; immunology ; Receptors, Interleukin-21 ; physiology

The role of cytokines and transcription factors on the regulation of megakaryocy topoiesis and platelet production are reviewed in this article. Megakaryocytopoiesis involves the proliferation and differentiation of megakaryocytic pro genitor cells into immature megakaryocytes, and the differentiation of immature megakaryocytes to mature megakaryocytes which produce platelets. The former is regulated mainly by thrombopoietin (TPO) and to a lesser degree by other cytokines such as interleukin-1 (IL-1), IL-3 and platelet-derived growth factor (PDGF), the later by TPO and probably IL-6 and IL-11. A number of transcription factors have been implicated in the control of megakaryocyte differentiation. GATA-1, FOG-1 and Fli-1 are essential regulators in early- and mid-stages of megakaryocytopoiesis. NF-E2 regulates late-stage of megakaryocytopoiesis and platelet production. However, the platelet release mechanism is poorly understood. Nitric oxide (NO) may act in the stage of platelet release through induction of apoptosis in megakaryocytes.
Animals ; Cytokines ; physiology ; DNA-Binding Proteins ; physiology ; Erythroid-Specific DNA-Binding Factors ; GATA1 Transcription Factor ; Hematopoiesis ; Humans ; Interleukins ; physiology ; Megakaryocytes ; physiology ; NF-E2 Transcription Factor ; NF-E2 Transcription Factor, p45 Subunit ; Platelet-Derived Growth Factor ; physiology ; Thrombopoiesis ; physiology ; Thrombopoietin ; physiology ; Transcription Factors ; physiology

OBJECTIVETo investigate the effect of melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) on the hepatocellular carcinoma cell lines and normal liver cell line in vitro.

METHODSHepatocellular carcinoma cell lines HepG2, SMMC7721, Hep3B, MHCC97L, M6 and normal liver cell line L02 were infected with Ad.mda-7. The gene expression of mda-7/IL-24 in these cell lines was confirmed by RT-PCR and ELISA assay. MTT assay and flow cytometry were used to study tumor cell proliferation and cell cycle in vitro. Hoechst staining and cytometry assay after Annexin-V and PI staining were studied to indicate the apoptosis effect.

RESULTSIt was confirmed by RT-PCR that the exogenous mda-7/IL-24 gene expressed in all of these cells. The mda-7/IL-24 protein product was confirmed by assaying the supernatant with ELISA. MTT and apoptosis test indicated mda-7/IL-24 can induce the hepatocellular carcinoma cell lines growth suppression, apoptosis in vitro but not in normal liver cell line L02, cell cycle test revealed mda-7/IL-24 can block cancer cell lines in G2/M but not in L02.

CONCLUSIONSmda-7/IL-24 selectively induces growth suppression, apoptosis in hepatocellular carcinoma lines but not in normal liver cell in vitro.

Adenoviridae ; genetics ; Apoptosis ; genetics ; physiology ; Carcinoma, Hepatocellular ; genetics ; pathology ; physiopathology ; Cell Cycle ; genetics ; physiology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation ; Genetic Vectors ; Hepatocytes ; cytology ; Humans ; Interleukins ; genetics ; physiology ; Liver Neoplasms ; genetics ; pathology ; physiopathology ; Transfection

AIMTo investigate if interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10), interferon-gamma (IFN-gamma) or tumor necrosis factor-alpha (TNF-alpha) are able to stimulate the level of lipid peroxidation of sperm membranes, either alone or in the presence of leukocytes.

METHODSSemen samples from normozoospermic donors were prepared by density gradient. The sperms were exposed to the indicated cytokines, at physiological and infection-inflammation concentrations, in the absence or presence of leukocytes. Lipid peroxidation of the sperm membranes was determined by measuring malondialdehyde (MDA) and 4-hydroxialkenals (HAE) formation.

RESULTSTNF-alpha, IL-8 and IFN-gamma increased the level of sperm membrane lipid peroxidation when tested at physiological concentrations. At infection-inflammation concentrations, only IL-8 was able to produce a higher effect. When assayed in the presence of leucocytes, IL-8 and TNF-alpha showed a higher effect at infection-inflammation concentrations than at physiological concentrations. Finally, IL-8 showed a higher effect in the presence of leukocytes than in their absence at both physiological and infection-inflammation concentrations. TNF-alpha also showed a higher effect when assayed in the presence of leukocytes than in their absence, but only at infection-inflammation concentrations. There was no effect of IL-6 or IL-10 in any of the tested conditions.

CONCLUSIONSeveral pro-inflammatory cytokines at physiological concentrations increase the level of lipid peroxidation of sperm membranes, which could be important for the sperm fecundation process. However, infection-inflammation concentrations of some cytokines, such as IL-8 and TNF-alpha, either alone or in the presence of leukocytes, could drive the lipid peroxidation of the spermatozoa plasma membrane to levels that can affect the sperm fertility capacity.

Cytokines ; analysis ; Humans ; Inflammation ; physiopathology ; Interferon-gamma ; metabolism ; Interleukins ; metabolism ; Leukocyte Count ; Lipid Peroxidation ; Male ; Reference Values ; Spermatozoa ; physiology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the effect of hIL-24 gene on proliferation, migration and invasion activity of human keloid fibroblasts (KFs).

METHODShIL-24 gene was cloned into lentivirus vector, then the lentivirus particles expressing hlL-24 were infected into KF cells. Real-time PCR and Western blot were performed to examine the expression of hIL-24 in lentivirus infected cells. The growth ability was detected by MTT assay. The cell cycle was analyzed by flow cytometry, The invasion and migration were detected by matrigel invasion assay and wound healing assay.

RESULTSComparing to controls group and KF-NC group, the expression levels of hIL-24 mRNA and protein were both significantly up-regulated after 4 days of hIL-24 lentivims infection. Comparing with the KF-NC group, MTT assay showed that the A490 of KF-hlL-24 group was down-regulated after lentivims infection ( P < 0. 05 ). Comparing with the KF-NC group, Cell cycle test revealed hlL-24 gene could block KF cells in G1 [(75. 40 ±2. 10)% ] , the proportion of KF cells was decreased in S phase [(4. 96 ± 1. 60)% ] and G2 phase [(0.01 ± 0.01)% ]. After KF cells were infected(P <0.01). Transfection of hlL-24 lentivirus inhibited the migration and invasion activity of KF cells.

CONCLUSIONLentivirus-mediated hlL-24 gene efficiently inhibits proliferation, cell cycle progression, migration and invasion activity of KF cells.

Cell Cycle ; Cell Line, Tumor ; Cell Movement ; genetics ; Cell Proliferation ; genetics ; Down-Regulation ; Fibroblasts ; physiology ; virology ; Genetic Vectors ; Humans ; Interleukins ; genetics ; physiology ; Keloid ; genetics ; pathology ; Lentivirus ; RNA, Messenger ; metabolism ; Transfection ; methods

BACKGROUNDInterleukin (IL)-27 has been reported to have anti-proliferate and anti-angiogenic activities on cancer cells. However, the involvement of IL-27 in malignant pleural effusion (MPE) remains unknown. Thus, in this research, we compared the immune functions of IL-27, interferon (IFN)-γ, and IL-17 on lung cancer cells and revealed the regulatory mechanism of IL-27 in MPE.

METHODSThe distribution of IL-27 in both MPE and blood was evaluated by enzyme-linked immunosorbent assay and flow cytometry. The expressions of cytokine receptors and the levels of the phosphorylated signal transducer and activator of transcription (STAT) signalings were detected by flow cytometry. As well as the effects of proliferation, apoptosis, migration, and adherent activity of IL-27, IFN-γ, and IL-17 on lung cancer cells were also explored.

RESULTSThe expression of IL-27 was increased in MPE when compared with blood (147.3 ± 25.1 pg/ml vs. 100.3 ± 13.9 pg/ml, P = 0.04). IL-27 was noted to suppress both proliferation (18.33 ± 0.21 vs. 27.77 ± 0.88, P = 0.0005) and migration (1.82 ± 0.44 vs. 3.13 ± 0.07, P = 0.04) of A549 cells, but obviously promoted apoptosis of A549 cells (9.47 ± 1.14 vs. 4.96 ± 0.17, P = 0.02) by activating STAT1 signaling. Interestingly, IL-27 played totally opposite effects on A549 cells by activating STAT3 pathway. Moreover, IL-27 exerted different intercellular adherent activities of A549 cells to pleural mesothelial cell monolayer by activating different STAT signalings.

CONCLUSIONSIL-27 might exert an important immune regulation on lung cancer cells in human pleural malignant environment.

Adult ; Aged ; Aged, 80 and over ; Cell Line ; Cell Movement ; genetics ; physiology ; Cell Proliferation ; genetics ; physiology ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Interleukins ; metabolism ; Lung Neoplasms ; metabolism ; Male ; Middle Aged ; Pleural Effusion, Malignant ; metabolism ; Signal Transduction