This work was aimed to investigate the effect of quinacrine on peripheral granulocytes and lymphocytes, interleukin 1 (IL-1) and interleukin 6 (IL-6) in peripheral blood serum of inflammatory reaction induced by microwave irradiation, and observe the protective effect of quinacrine against microwave irradiation injury. BALB/c mice were suffered from microwave irradiation with the total intensity of 50 mW/cm(2) for 30 minutes, at 1 hour before irradiation quinacrine (12.6 mg/kg or 50.4 mg/kg) was orally administrated. Mice received same volume of water for injection instead of quinacrine were named as microwave irradiation group (MR group), and mice received no microwave irradiation but stayed in microwave irradiation environment also for 30 min were set as control. After microwave irradiation, mice were sacrificed and peripheral blood cells were analyzed with cytoanalyzer, and mice serum interleukin-1β, interleukin-6 were detected by radioimmunoassay. The results showed that microwave irradiation increased the count of peripheral granulocytes and lymphocyte along with prolongation of time, while the increase of these cells in mice administrated quinacrine was markedly delayed. The level of IL-1β in serum of mice was significantly increased after 1 day of microwave irradiation (50 mW/cm(2)), and recovered to normal level after 7 days. The 2 concentrations of quinacrine (12.6 mg/kg, 50.4 mg/kg) could suppress level of IL-1β in serum induced by microwave irradiation. The level of IL-6 in serum of mice was gradually increased after microwave irradiation with intensity of 50 mW/cm(2) for 7 days, but quinacrine administration could delay the rise of IL-6 level, specially within time of 2 days. It is concluded that the quinacrine administration can delay the increase of peripheral granulocytes and lymphocytes inducted by microwave irradiation, and may partially suppress the rise of IL-1β and IL-6 in serum. The results of this study suggest that the quinacrine can provide some protective effect against microwave irradiation injury.
Animals ; Inflammation ; Interleukin-1 ; blood ; Interleukin-1beta ; blood ; Interleukin-6 ; blood ; Leukocyte Count ; Male ; Mice ; Mice, Inbred BALB C ; Microwaves ; adverse effects ; Quinacrine ; pharmacology

Protective effect of interleukin-1beta (IL-1beta) on motor neurons was studied after peripheral nerve injury. Twenty Wistar rats were divided into 2 groups randomly. The right sciatic nerve of each rat was resected. After silicon tubulization of sciatic nerve in rat, 15 microl 1 ng/ml IL-1beta and PBS solution were injected into the silicon capsule respectively. Enzyme histochemistry was performed to show acetyle cholesterase (AchE) and nitric oxide staining (NOS) activity of spinal alpha motor neurons in spinal segments 2 weeks later. Neurons were counted and the diameter and cross sectional (c/s) area of neurons were analyzed by using computer image analysis system. The results showed that as compared with the normal side, both enzyme activities significantly changed in motor neurons in PBS group. The diameter and c/s area of both neurons changed significantly too (P < 0.01). These results suggest that exogenous IL-1beta protects alpha-motor neurons from degeneration and necrosis after peripheral nerve injury.
Interleukin-1/*pharmacology ; Motor Neurons/*pathology ; Neuroprotective Agents/*pharmacology ; Random Allocation ; Rats, Wistar ; Sciatic Nerve/*injuries ; Spinal Cord/pathology

BACKGROUNDEpidermal burn injury may trigger significant apoptosis of the spleen cells, which might be caused by a burn-induced systemic inflammatory reaction. Heparin has been shown to possess anti-inflammatory properties. Interleukin 1 (IL-1) is centrally important among pro-inflammatory cytokines. We hypothesized that heparin might inhibit burn-induced apoptosis in the spleen via suppression of the IL-1 pathway.

METHODSBurn injury was performed on IL-1 R+/+ ( IL-1 receptor wild-type mouse) and IL-1 R-/- (IL-1 receptor knock-out mouse) mice, and they were then treated with heparin, saline or IL-1 receptor antagonist IL-Ra. Apoptosis, IL-1α and IL-1β expression were assessed in the spleens and serum. Survival curve analysis was further applied to elucidate the mechanism of heparin's protective properties.

RESULTSBurn induced significant apoptosis (sham: 3.6%± 2.1% vs. burn: 28.8%± 5.9%; P < 0.001) and remarkable expression o IL-1α and IL-1β in the mouse spleens and serum. Heparin reduced the burn-induced apoptosis in the spleens (heparin treated: 8.6%± 3.4%, P < 0.005), which could be blocked by IL-1Ra. Heparin markedly decreased both IL-1α and IL-1β expression in the spleens and serum of burned mice. IL-1 R-/- mice demonstrated considerably less apoptosis in the spleens and had a higher survival rate after burns. Heparin did not significantly decrease apoptosis in the spleen and the mortality rate in IL-1 R-/- mice after burns.

CONCLUSIONHeparin inhibits burn-induced apoptosis of the spleen cells by suppressing IL-1 expression in mice.

Animals ; Apoptosis ; drug effects ; Burns ; drug therapy ; metabolism ; Heparin ; therapeutic use ; Interleukin 1 Receptor Antagonist Protein ; pharmacology ; Interleukin-1 ; metabolism ; Male ; Mice ; Mice, Knockout ; Receptors, Interleukin-1 ; metabolism ; Spleen ; drug effects ; metabolism

The present study was to investigate the effects of intracerebroventricular (i.c.v.) injection of interleukin-1beta (IL-1beta) on thermal nociception in SD rats. The rats were divided into control and drug-administration groups. The animals of control group were given vehicle solution via i.c.v. injection. The animals of drug-administered groups were given IL-1beta at different doses (5, 50 and 500 pg/kg b.w.) via i.c.v. injection. IL-1 receptor antagonist (IL-1ra, 50 ng/kg) was injected 20 min before injection of IL-1beta or vehicle solution. The nociceptive threshold, which was represented as paw withdrawal latency (PWL), to a noxious thermal stimulation was measured using an analgesiameter. I.c.v. injection of IL-1beta dose-dependently shortened the PWL. At the dose of 500 pg/kg, the shortening of the PWL occurred at 20 min, reaching a peak within 40 min, lasted 100 min after injection, then gradually returned to the baseline level. Pretreatment with IL-1ra completely blocked the effects of IL-1beta-induced shortening in PWL. The results obtained suggest that IL-1beta may induce hyperalgesia in rats through binding to IL-1 receptors in the brain.
Animals ; Hot Temperature ; Hyperalgesia ; drug therapy ; Injections, Intraventricular ; Interleukin 1 Receptor Antagonist Protein ; pharmacology ; Interleukin-1beta ; pharmacology ; Nociception ; Rats ; Rats, Sprague-Dawley ; Receptors, Interleukin-1 ; antagonists & inhibitors ; metabolism ; Touch

OBJECTIVES: To investigate the possible role of mononuclear cells and their products in the pathogenesis of IgA nephropathy, in vitro expression of ICAM-1 on cultured mouse mesangial cell (MC) was examined after stimulation with mononuclear cell culture supernatant from patients with IgA nephropathy. METHODS: Peripheral blood mononuclear cells (PBMC) were isolated and cultured from 18 patients with primary IgA nephropathy, 8 normal controls and 5 patients with non-IgA nephropathy (FSGS 1, MGN 3, MPGN 1). ICAM-1 expression on cultured mouse MC by TNF-alpha, IL-1 beta and culture supernants of PBMC were analyzed using a cell ELISA method. The concentration of IL-1 beta and TNF-alpha in culture supernatants was measured by using a commercially available radioimmunoassay kit. RESULTS: Addition of human recombinant TNF-alpha induced an increased ICAM-1 expression in a dose-dependent manner. The expression of ICAM-1 was further increased after co-stimulation with TNF-alpha and IL-1 beta. Addition of PBMC culture supernatants into mouse MC induced significantly higher expression of ICAM-1 by supernatants from the patients with IgA nephropathy compared with that from normal controls. The concentration of TNF-alpha and IL-1 beta in supernatants from the patients with IgA nephropathy was significantly higher than that from those with non-IgA nephropathy. CONCLUSION: TNF-alpha and IL-1 released from mononuclear cells induced the up-regulation of ICAM-1 expression and this may be related to the immune pathogenesis of IgA nephropathy.
Animal ; Cells, Cultured ; Glomerular Mesangium/immunology ; Glomerular Mesangium/cytology ; Glomerulonephritis, IGA/immunology* ; Glomerulonephritis, IGA/etiology ; Human ; Intercellular Adhesion Molecule-1/metabolism* ; Interleukin-1/secretion ; Interleukin-1/pharmacology ; Leukocytes, Mononuclear/immunology ; Mice ; Tumor Necrosis Factor/secretion ; Tumor Necrosis Factor/pharmacology

Animals ; Cells, Cultured ; Interleukin-1 ; pharmacology ; Matrix Metalloproteinase 1 ; secretion ; Muscle, Smooth, Vascular ; cytology ; Myocytes, Smooth Muscle ; cytology ; drug effects ; metabolism ; Platelet-Derived Growth Factor ; pharmacology ; Rabbits

OBJECTIVETo investigate the influence of baicalin on the IL-1beta induced pro-MMP-1 in HGF and the effects of baicalin on MMP-3 expression in periodontal ligament cells (PDLCs).

METHODSThe amount of secreted pro-MMP-1 and MMP-3 expression was detected by ELISA and cell immunochemistry.

RESULTS(1) The amount of secreted pro-MMP-1 (3.333 +/- 0.123) microg/L increased significantly following 1 microg/L of IL-1beta, compared with control group (1.960 +/- 0.180) microg/L. Addition of baicalin to cell culture medium for 1 hour following IL-1beta decreased pro-MMP-1 secretion in a dose-dependent manner in the range of 10 approximately 1,000 microg/L. (2) 1 microg/L IL-1beta could significantly stimulate the synthesis and secretion of MMP-3 in PDLCs. (3) The baicalin could not interfere the synthesis of MMP-3, but could inhibit the release of MMP-3 from PDLCs.

CONCLUSIONSBaicalin could inhibit the secretion of pro-MMP-1 and MMP-3 expression in IL-1beta induced HGF and PDLCs, which suggests that baicalin may play an important role in preventing and treating periodontal disease.

Collagenases ; biosynthesis ; genetics ; Enzyme Precursors ; biosynthesis ; genetics ; Fibroblasts ; enzymology ; pathology ; Flavonoids ; pharmacology ; Gingiva ; enzymology ; pathology ; Humans ; Interleukin-1 ; pharmacology ; Interleukin-1beta ; Matrix Metalloproteinase 1 ; Metalloendopeptidases ; biosynthesis ; genetics ; Peptide Fragments ; pharmacology ; Periodontal Ligament ; enzymology ; pathology ; Periodontitis ; enzymology ; pathology ; Scutellaria ; chemistry

Objective To explore the effect and mechanism of hesperidin in treating the lung injury in the mouse model of respiratory syncytial virus (RSV)-induced bronchiolitis. Methods A mouse model of RSV-induced bronchiolitis was established,and 60 BALB/c mice were assigned into a control group,a model group,a low-dose hesperidin (18 mg/kg) group,a high-dose hesperidin (36 mg/kg) group,and a high-dose hesperidin (36 mg/kg)+Jagged1(1 mg/kg) group by random number table method,with 12 mice in each group. Corresponding doses of drugs were administrated for intervention,and the control group and model group were administrated with the same amount of saline.The bronchoalveolar lavage fluid (BALF) samples were collected and alveolar macrophages were isolated.ELISA was employed to detect the levels of interleukin (IL)-4,IL-6,tumor necrosis factor-α (TNF-α),and IL-10 in BALF,and flow cytometry to detect the M1/M2 polarization of macrophages.qRT-PCR and Western blotting were respectively conducted to detect the mRNA and protein levels of inducible nitric oxide synthase (iNOS),arginase 1 (Arg-1),Jagged1,and Notch1 in the lung tissue. Results Compared with the control group,the modeling of RSV-induced bronchiolitis elevated the IL-4,IL-6,and TNF-α levels,increased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and up-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.001).Meanwhile,the modeling lowered the IL-10 level,decreased the proportion of M2-type macrophages,and down-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Compared with the model group,low- and high-dose hesperidin lowered the IL-4,IL-6,TNF-α levels,decreased the proportion of M1-type macrophages and the lung inflammation and mucus secretion scores,and down-regulated the mRNA and protein levels of iNOS,Jagged1,and Notch1 in BALF (all P<0.05).Moreover,hesperidin elevated the IL-10 level,increased the proportion of M2-type macrophages,and up-regulated the mRNA and protein levels of Arg-1 (all P<0.001).Using recombinant Jagged1 protein to activate Notch1 signaling pathway can significantly attenuate the promotion of high-dose hesperidin on M2 macrophage polarization and amelioration of lung inflammation damage (all P<0.01). Conclusion Hesperidin may alleviate the lung inflammation damage in mice with RSV-induced bronchiolitis by inhibiting the Jagged1/Notch1 signaling pathway and promoting the M2-type polarization of macrophages.
Animals ; Mice ; Bronchiolitis/metabolism* ; Hesperidin/metabolism* ; Interleukin-10/pharmacology* ; Interleukin-4/pharmacology* ; Interleukin-6/metabolism* ; Jagged-1 Protein/pharmacology* ; Lung Injury/metabolism* ; Macrophages ; Mice, Inbred BALB C ; RNA, Messenger/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Nitric oxide (NO) has been considered as an important mediator in inflammatory phases and in loss of cartilage. In inflammatory arthritis, NO levels are correlated with disease activity and articular cartilage is able to produce large amounts of NO with the appropriate inducing factor such as cytokines. The old animals are shown to have a greater sensitivity to NO than young animals. This study evaluated the basal production of NO in normal and OA-affected chondroyctes from young and old patients and compared the levels of NO formation in response to IL-1beta. The results showed that the basal levels were 7-fold higher in old chondrocytes than those of young cells. However, the IL-1beta induced NO production was seen to decrease with age. Aminoguianidine (AG), a competitive inhibitor of iNOS, inhibited NO formation completely in both chondrocytes from young and old individuals. However, at the same concentration of AG it caused partial inhibition of NO and iNOS formation in chondrocytes from OA-affected individuals. In addition, although the IL-1beta induced NO production was much lesser than that of young chondrocytes, the inhibition of collagen production by IL-1beta was prominent in old chondrocytes and OA-affected chondrocytes. These results suggest that age-related differences in the regulation of NO production and collagen production, which may affect the ageing cells and osteoarthritic changes in some way.
Aging/*physiology ; Cartilage, Articular/*physiopathology ; Cells, Cultured ; Chondrocytes/*metabolism ; Collagen Type II/metabolism ; Enzyme Inhibitors/pharmacology ; Guanidines/pharmacology ; Human ; Interleukin-1/pharmacology ; Nitric Oxide/*biosynthesis ; Osteoarthritis/*metabolism

Nitric oxide (NO) has been considered as an important mediator in inflammatory phases and in loss of cartilage. In inflammatory arthritis, NO levels are correlated with disease activity and articular cartilage is able to produce large amounts of NO with the appropriate inducing factor such as cytokines. The old animals are shown to have a greater sensitivity to NO than young animals. This study evaluated the basal production of NO in normal and OA-affected chondroyctes from young and old patients and compared the levels of NO formation in response to IL-1beta. The results showed that the basal levels were 7-fold higher in old chondrocytes than those of young cells. However, the IL-1beta induced NO production was seen to decrease with age. Aminoguianidine (AG), a competitive inhibitor of iNOS, inhibited NO formation completely in both chondrocytes from young and old individuals. However, at the same concentration of AG it caused partial inhibition of NO and iNOS formation in chondrocytes from OA-affected individuals. In addition, although the IL-1beta induced NO production was much lesser than that of young chondrocytes, the inhibition of collagen production by IL-1beta was prominent in old chondrocytes and OA-affected chondrocytes. These results suggest that age-related differences in the regulation of NO production and collagen production, which may affect the ageing cells and osteoarthritic changes in some way.
Aging/*physiology ; Cartilage, Articular/*physiopathology ; Cells, Cultured ; Chondrocytes/*metabolism ; Collagen Type II/metabolism ; Enzyme Inhibitors/pharmacology ; Guanidines/pharmacology ; Human ; Interleukin-1/pharmacology ; Nitric Oxide/*biosynthesis ; Osteoarthritis/*metabolism