OBJECTIVETo investigate the changes of cytokines in induced sputum at different stages of silicosis patients.

METHODSA total of 200 workers from one of the Shandong Province gold mine were chosen as object of observation. Among which 40 patients at silicosis stage I and 40 patients at silicosis stage II were divided into silicosis observed object group, silicosis stage I group, silicosis stage II group, and another 80 workers exposed to silica dust without suffering from silicotic Clinical symptoms, however, were chosen as group of dust exposed, and 40 logistical workers without being exposed and history of silicosis's illness were chosen as control group. And ask their basic information by questionnaire. Then, spray-inhalation the induced sputum and apply the ELISA to assess the level of tumor necrosis factor (TNF), interleukin (IL), macrophage inflammatory protein-1 (MIP-1α), monocyte chemotactic factor-1 (MCP-1), metalloproteinases (MMP), transforming growth factor-β (TGF-β), platelet derived growth factor (PDGF) in induced sputum from subjects.

RESULTSThe level of TGF-β [(901.60 ± 30.09) ng/L] in the induced sputumof patients in silicosis stage I group is lower than that in the observed object group [(913.02 ± 20.51) ng/L], and the level of MMP-9 [(212.49 ± 5.97) ng/L], MCP-1 [(129.91 ± 4.30) ng/L] has various degrees of increase than that in control group, observed object group and dust exposed group. All the differences have statistical significances (P < 0.05). The level of TNF-α [(85.76 ± 3.78) ng/L] in the induced sputum of patients in silicosis stage I group reaches the maximum, there are significant differences comparing with that level in the silica dust exposure group and the control group, whose differences are statistically significant (P < 0.05). Compared with the control group, the level of MMP-2 (427.95 ± 23.64) in the induced sputum of patients in silicosis stage I group has increased, whose differences also have statically significant (P < 0.05). Compared with the control group, silica dust exposed group, the observation group of objects, the pneumosilicosis patients of IL-16 in induced sputum IL-16 (21.40 ± 9.24) decreased, the content of PDGF [(5.96 ± 0.51) ng/L], MMP-2 [(447.86 ± 27.10) ng/L], MMP-9 [(223.91 ± 12.28) ng/L], MCP-1 [(122.87 ± 6.08) ng/L] increased, the differences are statistically significant (P < 0.05).

CONCLUSIONAs silicosis biomarkers, TNF-alpha, TGF-beta, IL-16, PDGF, MMP-2, MMP-9 and MCP-1 have certain significance, further suggesting that early detection rate of patients with silicosis can be improved by employing the multiple indexes discriminate equation.

Biomarkers ; metabolism ; Case-Control Studies ; Chemokine CCL2 ; metabolism ; Chemokine CCL3 ; metabolism ; Cytokines ; metabolism ; Discriminant Analysis ; Dust ; Humans ; Interleukin-16 ; metabolism ; Matrix Metalloproteinase 2 ; metabolism ; Matrix Metalloproteinase 9 ; metabolism ; Platelet-Derived Growth Factor ; metabolism ; Silicosis ; diagnosis ; Sputum ; chemistry ; Transforming Growth Factor beta ; metabolism ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo culture osteoblast in vitro and evaluate CCL3 receptor CCR1 expression in patients with multiple myeloma (MM).

METHODSBone marrow osteoblasts from MM patients were cultured in vitro with dexamethasone, β-sodium glycerophosphate and vitamin C, which were identified by alkaline phosphatase staining, Von Kossa's staining. The CCL3 receptor expression was evaluated by flow cytometry. The morphology and quantity of osteoblast were observed after exposure to CCL3.

RESULTSBone marrow osteoblasts from MM patients could be cultured in vitro and be identified by positive staining of alkaline phosphatase and Von Kossa's. MM-derived osteoblasts expressed higher levels of CCR1 (74.48 ± 7.31)%, compared with normal controls (48.35 ± 8.81)%. Calcium deposition of osteoblasts after exposure to CCL3 was less than that of controls.

CONCLUSIONBone marrow osteoblasts could be cultured in vitro from MM Patients. CCL3 may contribute to the development of myeloma bone disease.

Adult ; Aged ; Cells, Cultured ; Chemokine CCL3 ; pharmacology ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; pathology ; Osteoblasts ; cytology ; drug effects ; metabolism ; Receptors, CCR1 ; metabolism ; Young Adult

This study was purposed to explore the mechanism of central nervous system (CNS) leukemia resulting from brain metastasis of human acute T-cell leukemia (T-ALL) cells and the role of MIP-1α in migration of Jurkat cells through human brain microvascular endothelial cells (HBMEC). The real-time PCR, siRNA test, transendothelial migration test, endothelial permeability assay and cell adhesion assay were used to detect MIP-1α expression, penetration and migration ability as well as adhesion capability respectively. The results showed that the MIP-1α expression in Jurkat cells was higher than that in normal T cells and CCRF-HSB2, CCRF-CEM , SUP-T1 cells. The MIP-1α secreted from Jurkat cells enhanced the ability of Jurkat cells to penetrate through HBMEC, the ability of Jurkat cells treated by MIP-1α siRNA to adhere to HBMEC and to migrate trans endothelial cells decreased. It is concluded that the MIP-1α secreted from Jurkat cells participates in process of penetrating the Jurkat cells through HBMEC monolayer.
Brain Neoplasms ; pathology ; secondary ; Cell Adhesion ; Cell Movement ; Chemokine CCL3 ; metabolism ; Endothelial Cells ; pathology ; Endothelium, Vascular ; pathology ; Humans ; Jurkat Cells ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma ; pathology

OBJECTIVETo explore the mechanism of Xiaoai Jiedu Recipe (XJR) for fighting against tumors by detecting tumor gene expression profiles of H22 tumor-bearing mice.

METHODSH22 tumor-bearing mice were randomly divided into the normal control group, the low dose XJR group, the medium dose XJR group, the high dose XJR group, and the Cisplatin group. The differentially expressed genes of tumor tissues in H22 tumor-bearing mice were detected by using gene chip technique. The antitumor mechanism of XJR associated signaling pathways and gene expressions were found out by pathway analysis. The chemokine signaling pathways were analyzed.

RESULTSXJP could significantly affect multiple signaling pathways associated with tumor growth, apoptosis, and immunity. XJP also could decrease expressions of CCL3 and CXCL2 in the chemokine signaling pathway.

CONCLUSIONXJP could inhibit the growth and invasion of tumor cells possibly by affecting expressions of some genes in the chemokine signaling pathway.

Animals ; Cell Line, Tumor ; Chemokine CCL3 ; metabolism ; Chemokine CXCL2 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; Gene Expression Profiling ; Liver Neoplasms, Experimental ; genetics ; metabolism ; Mice ; Mice, Inbred ICR ; Signal Transduction ; drug effects

OBJECTIVETo explore the protective mechanism of Fengshiqing Recipe (FR) against bone destruction in collagen-induced arthritis (CIA) rats.

METHODSRats were divided into four groups in the experiment,i.e., the blank control group, the model group, the MTX group (MTX, 1 mg/1 000 g), and the FR group (24 g crude FR/kg). The CIA model was prepared except the blank control group. Medication was started in the MTX group and the FR group from the 14th day after modeling to the 56th day. The toe volume was measured on every Tuesday and Friday. Expression levels of serum IL-17, RANKL, MIP-1alpha were detected after 3-and 6-week intervention. The bone scintigraphy with nuclide (SPECT), bone mineral density (BMD), and the pathological section were observed to assess the intervention of drugs of heat clearing blood activating actions in the bone destruction of CIA rats.

RESULTSFrom the 10th day of modeling, the volume of both toes started to swell and reached the peak at about 21 days. It was obviously shrunk at about 30 days. Of them, the swelling degree was milder in the MTX group and the FR group than in the model group. Compared with the model group at the same phase, the levels of IL-17 and RANKL decreased in the MTX group after 3 weeks of intervention (P < 0.01, P < 0.05). The IL-17 level decreased in the FR group after three weeks of intervention (P < 0.05). The RANKL level decreased in the MTX group and the FR group after 6 weeks of intervention (P < 0.01, P < 0.05). Compared with the model group and the MTX group, the overall BMD and ankle BMD increased in the FR group after 6 weeks of intervention (P < 0.01, P < 0.05). The ankle ROI/mandible and the toe ROI/mandible were elevated in the FR group after 3 weeks of intervention (P < 0.05). Pathological results suggested that the joint lacunae was significantly widened, the hyperplasia of the synovial tissue was so severe, and the bone tissue was destroyed in the model group. Compared with the model group, the aforesaid conditions were significantly improved in the MTX group and the FR group. The cartilage structure was complete.

CONCLUSIONQR could inhibit decreased BMD, prevent bone destruction, which might be achieved by down-regulating expression levels of IL-17, RANKL, and MIP-1alpha through the osteo immunological Th/RANKL system,inhibiting maturation and differentiation of osteoclasts, thereby, inhibiting bone destruction.

Animals ; Arthritis, Experimental ; drug therapy ; metabolism ; Bone Density ; Bone and Bones ; drug effects ; pathology ; Chemokine CCL3 ; metabolism ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Female ; Interleukin-17 ; metabolism ; RANK Ligand ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the changes in the levels of inflammatory cytokines in bronchoalveolar lavage fluid (BALF) in rats exposed to silica dust.

METHODSExperimental rats were randomly divided into control group and three experimental groups (doses of dust: 15, 30, and 60 mg/ml), with 42 rats in each group. Each rat in the control group was treated with 1 ml of normal saline by intratracheal instillation, while each rat in the experimental groups was exposed to 1 ml of silica suspension by a single intratracheal instillation. Seven rats in each group were killed at 1, 3, 7, 14, 21, and 28 days after exposure, and then BALF was collected. Enzyme-linked immunosorbent assay was used to measure the levels of interleukin (IL)-1, IL-6, IL-16, macrophage inflammatory protein-1 alpha (MIP-1α), monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β).

RESULTSThe levels of cytokines in each experimental group were higher than those in the control group at any time point. In the early stage of exposure (day 1-3), BALF IL-1 level increased significantly with the increase in dust dose, and on day 14, BALF IL-6 and IL-16 levels increased significantly with the increase in dust dose; the levels of IL-1, IL-6, and IL-16 in the experimental groups reached the peak on day 14. There were significant differences in the levels of MIP-1α and MCP-1 between the experimental groups (FMIP-1α = 30.106, P<0.01; FMCP-1 = 17.193, P<0.01). In each group, the level of MCP-1 varied significantly at different time points (F = 0.618, P>0.05). On day 1-14, BALF TNF-α level increased with the increase in dust dose, with a significant dose-response relationship (P < 0.05). In each experimental group, TNF-α level reached the peak on day 14. On days 14, 21, and 28, the high-dose group had significantly higher BALF TGF-β levels than the low-dose group (P<0.05); on days 14 and 28, the high-dose group had significantly higher BALF TGF-β levels than the middle-dose group (P<0.05).

CONCLUSIONIL-1, IL-6, IL-16, MIP-1α, MCP-1, and TNF-α play a role in the development and progression of silicosis inflammation. TGF-β may be related to (related to; associated with; correlated with) fibrosis.

Animals ; Bronchoalveolar Lavage Fluid ; chemistry ; Chemokine CCL2 ; metabolism ; Chemokine CCL3 ; metabolism ; Cytokines ; metabolism ; Interleukin-1 ; metabolism ; Interleukin-16 ; metabolism ; Interleukin-6 ; metabolism ; Rats ; Rats, Wistar ; Silicon Dioxide ; toxicity ; Silicosis ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo detect the mRNA and protein expressions of MIP-1alpha in EPS and determine their significance in the sub-typing of chronic prostatitis.

METHODSWe collected samples of expressed prostatic secretion (EPS) from 50 cases of chronic prostatitis, including 16 cases of chronic bacterial prostatitis (CBP), 23 cases of chronic nonbacterial prostatitis/chronic pelvic pain syndrome (CPPS) (11 CPPS IIIA, 12 CPPS IIIB), and 11 cases of type-IV asymptomatic inflammatory prostatitis (AIP). Another 15 healthy volunteers were included as normal controls. The mRNA and protein levels of MIP-1alpha in EPS were determined by RT-PCR and ELISA, respectively, followed by statistical analysis with SPSS 15.0.

RESULTSThe mRNA expression of MIP-1alpha was markedly higher in the CPPS IIIA and CPPS IIIB groups than in the others (P<0.05). The protein level of MIP-1alpha was (1174.3 +/- 89.2) pg/ml in CPPS IIIA and (842.3 +/- 76.2) pg/ml in CPPS IIIB, significantly higher than (198.0 +/- 37.8) pg/ml in the control, (347.0 +/- 61.6) pg/ml in CBP and (292.0 +/- 56.4) pg/ml in type-IV AIP (P<0.05).

CONCLUSIONDetermination of mRNA and protein levels of MIP-1alpha in EPS may help the sub-typing and diagnosis of chronic prostatitis.

Adult ; Aged ; Body Fluids ; metabolism ; Case-Control Studies ; Chemokine CCL3 ; metabolism ; Chronic Disease ; Humans ; Male ; Middle Aged ; Prostate ; secretion ; Prostatitis ; metabolism ; Young Adult

Toxoplasma gondii can modulate host cell gene expression; however, determining gene expression levels in intermediate hosts after T. gondii infection is not known much. We selected 5 genes (ALDH1A2, BEX2, CCL3, EGR2 and PLAU) and compared the mRNA expression levels in the spleen, liver, lung and small intestine of genetically different mice infected with T. gondii. ALDH1A2 mRNA expressions of both mouse strains were markedly increased at day 1-4 postinfection (PI) and then decreased, and its expressions in the spleen and lung were significantly higher in C57BL/6 mice than those of BALB/c mice. BEX2 and CCR3 mRNA expressions of both mouse strains were significantly increased from day 7 PI and peaked at day 15-30 PI (P<0.05), especially high in the spleen liver or small intestine of C57BL/6 mice. EGR2 and PLAU mRNA expressions of both mouse strains were significantly increased after infection, especially high in the spleen and liver. However, their expression patterns were varied depending on the tissue and mouse strain. Taken together, T. gondii-susceptible C57BL/6 mice expressed higher levels of these 5 genes than did T. gondii-resistant BALB/c mice, particularly in the spleen and liver. And ALDH1A2 and PLAU expressions were increased acutely, whereas BEX2, CCL3 and EGR2 expressions were increased lately. Thus, these demonstrate that host genetic factors exert a strong impact on the expression of these 5 genes and their expression patterns were varied depending on the gene or tissue.
Aldehyde Dehydrogenase/*genetics/metabolism ; Animals ; Brain/metabolism/parasitology ; Chemokine CCL3/*genetics/metabolism ; Early Growth Response Protein 2/*genetics/metabolism ; Gene Expression Profiling ; Humans ; Lung/metabolism/parasitology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred Strains ; Nerve Tissue Proteins/*genetics/metabolism ; Organ Specificity ; Spleen/metabolism/virology ; Toxoplasma/*physiology ; Toxoplasmosis/*genetics/metabolism/parasitology ; Urokinase-Type Plasminogen Activator/*genetics/metabolism

OBJECTIVESTo investigate the changes of nuclear factor (NF-)κBp65 and inflammatory chemotactic factors including monocyte chemoattractant protein 1 (MCP-1/CCL-2), macrophage inflammatory protein 1α (MIP-1α/CCL-3), glial fibrillary acidic protein (GFAP) in brains of the patients with Alzheimer's disease (AD) and reveal the correlation of these factors.

METHODSTen patients with AD and 8 age-matched control subjects were selected in the study. Immunohistochemistry was performed to determine the protein expression of NF-κBp65, MCP-1, MIP-1α and GFAP. Double-immunohistochemistry was used to detect the expression of GFAP and β-amyloid peptide 1-42 (Aβ(1-42)) in the hippocampus, temporal and frontal cortices.

RESULTSAs compared to age-matched controls (the numbers of the positively stained neuronal cells: 0.31 ± 0.20, 0.25 ± 0.20 and 0.25 ± 0.20, respectively), the immunoreactivities of NF-κBp65 in the hippocampus and the temporal and frontal cortices (numbers of the positively stained cells: 3.6 ± 1.5, 2.2 ± 1.2 and 2.2 ± 1.2, respectively) were significantly increased in AD brains. The levels of MCP-1 and MIP-1α in the hippocampus, and the temporal and frontal cortices (numbers of the positively stained neuronal cells: 8.0 ± 1.3, 8.8 ± 1.0, 9.3 ± 1.4, respectively;and 8.1 ± 1.5, 12.5 ± 1.1, 6.4 ± 1.1, respectively) with AD were significantly higher than those of controls (the numbers of the positive neuronal cells: 4.5 ± 0.9, 4.5 ± 0.6, 4.0 ± 1.8, respectively; and 5.0 ± 1.9, 6.3 ± 2.2, 3.8 ± 1.5, respectively). An increased number of glial cells stained with GFAP were observed to extensively distribute around the senile plaques in AD brains. There were significant correlations between NF-κBp65 and these inflammatory chemotactic factors in AD brains.

CONCLUSIONCorrelative expressions of NF and inflammatory chemotactic factors were found in the brains of AD patients, through a mechanism that may involve the inflammatory response induced by Aβ in the processing of AD.

Aged ; Aged, 80 and over ; Alzheimer Disease ; metabolism ; pathology ; Brain ; metabolism ; pathology ; Chemokine CCL2 ; metabolism ; Chemokine CCL3 ; metabolism ; Female ; Frontal Lobe ; metabolism ; pathology ; Glial Fibrillary Acidic Protein ; metabolism ; Hippocampus ; metabolism ; pathology ; Humans ; Immunohistochemistry ; Male ; Neuroglia ; metabolism ; pathology ; Plaque, Amyloid ; metabolism ; pathology ; Temporal Lobe ; metabolism ; pathology ; Transcription Factor RelA ; metabolism

Although 4,4'-diaminodiphenylsulfone (DDS, dapsone) has been used to treat several dermatologic conditions, including Hansen disease, for the past several decades, its mode of action has remained a topic of debate. We recently reported that DDS treatment significantly extends the lifespan of the nematode C. elegans by decreasing the generation of reactive oxygen species. Additionally, in in vitro experiments using non-phagocytic human fibroblasts, we found that DDS effectively counteracted the toxicity of paraquat (PQ). In the present study, we extended our work to test the protective effect of DDS against PQ in vivo using a mouse lung injury model. Oral administration of DDS to mice significantly attenuated the lung tissue damage caused by subsequent administration of PQ. Moreover, DDS reduced the local expression of mRNA transcripts encoding inflammation-related molecules, including endothelin-1 (ET-1), macrophage inflammatory protein-1alpha (MIP-1alpha), and transforming growth factor-beta (TGF-beta). In addition, DDS decreased the PQ-induced expression of NADPH oxidase mRNA and activation of protein kinase Cmicro (PKCmicro). DDS treatment also decreased the PQ-induced generation of superoxide anions in mouse lung fibroblasts. Taken together, these data suggest the novel efficacy of DDS as an effective protective agent against oxidative stress-induced tissue damages.
Animals ; Cells, Cultured ; Chemokine CCL3/drug effects/metabolism ; Dapsone/*administration & dosage ; Endothelin-1/drug effects/metabolism ; Fibroblasts/drug effects ; Herbicides/*antagonists & inhibitors/toxicity ; Lung Injury/chemically induced/*prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; Oxidative Stress ; Paraquat/*antagonists & inhibitors/toxicity ; Protective Agents/*administration & dosage ; Protein Kinase C/genetics/metabolism ; Superoxides/analysis ; Transforming Growth Factor beta/drug effects/metabolism