摘要
SUMMARY: The objective of this study was to observe the clinical efficacy of apatinib (AP) combined with 131I in the treatment of radioiodine-refractory differentiated thyroid cancer (RAIR-DTC) and the prognostic significance of MIP-1α after treatment, and to provide reference and guidance for future treatment and disease assessment of RAIR-DTC. One hundred and six patients with RAIR- DTC admitted to our hospital from January 2019 to October 2020 were selected for the study. All the patients were treated with TC surgery with 131I at our hospital, and 58 of them were subsequently transferred to AP treatment, which was considered as the research group; the other 48 patients were transferred to thyroid stimulating hormone (TSH) suppression treatment, which was considered as the control group. The clinical efficacy of the research group was better than that of the control group (P 0.05). After treatment, Tg, TL, maximum diameter of C/B lymph nodes, number of lymph nodes and number of calcified spots were lower in the research group than in the control group (P < 0.05). ROC analysis revealed that the predictive sensitivity of MIP-1α for prognosis of 3-year RAIR-DTC death in the research group of patients was 84.63 % and the specificity was 72.16 %. AP combined with 131I is effective in the treatment of RAIR-DTC and is worth using in the clinical practice. In addition, elevated levels of MIP-1α predicted a poor prognosis for patients with RAIR-DTC.
El objetivo de este estudio fue observar la eficacia clínica de apatinib (AP) combinado con 131I en el tratamiento del cáncer de tiroides diferenciado refractario al yodo radiactivo (RAIR-DTC) y la importancia pronóstica de MIP-1α después del tratamiento, y proporcionar referencia y orientación para futuros tratamientos y enfermedades. Evaluación de RAIR- DTC. Se seleccionaron para el estudio 106 pacientes con RAIR- DTC ingresados en nuestro hospital desde enero de 2019 hasta octubre de 2020. Todos los pacientes fueron tratados con cirugía CT con 131I, y 58 de ellos fueron trasladados posteriormente a tratamiento AP, los que fueron considerados como grupo de investigación; los otros 48 pacientes fueron transferidos a tratamiento de supresión de la hormona estimulante de la tiroides (TSH), que se consideró como grupo de control. La eficacia clínica del grupo de investigación fue mejor que la del grupo de control (P 0,05). Después del tratamiento, Tg, TL, diámetro máximo de los linfonodos C/B, número linfonodos y número de manchas calcificadas fueron menores en el grupo de investigación que en el grupo de control (P <0,05). El análisis ROC reveló que la sensibilidad predictiva de MIP-1α para el pronóstico de muerte por RAIR-DTC a 3 años en el grupo de pacientes de investigación fue del 84,63 % y la especificidad fue del 72,16 %. AP combinado con 131I es eficaz en el tratamiento del RAIR-DTC y vale la pena utilizarlo en la práctica clínica. Además, los niveles elevados de MIP-1α predijeron un mal pronóstico para los pacientes con RAIR- DTC.
Subject(s)
Humans , Pyridines/therapeutic use , Thyroid Neoplasms/therapy , Iodine Radioisotopes/therapeutic use , Antineoplastic Agents/therapeutic use , Prognosis , Thyroid Neoplasms/drug therapy , Thyroid Neoplasms/radiotherapy , Treatment Outcome , Combined Modality Therapy , Macrophage Inflammatory Proteins摘要
O Exército Brasileiro (EB) desenvolveu recentemente o método de treinamento físico militar Cross Operacional (CO), caracterizado por exercícios combinados aeróbios e resistidos de moderada/alta intensidade. O caráter de moderada/alta intensidade do CO pode levar ao comprometimento das fibras musculares, aumentando o risco de lesão e exacerbação de uma resposta inflamatória aguda. Nesse contexto, a análise de marcadores indiretos de dano muscular pode ser utilizada para avaliação do nível de intensidade do CO e recuperação pós-exercício. O objetivo desse estudo foi observar o efeito agudo do CO sobre os marcadores indiretos de dano muscular em militares do EB. Vinte e quatro militares voluntários, do sexo masculino, com idade média de 20,8 ± 1,8 anos participaram desse estudo. As quatro sessões correspondentes aos níveis do CO foram executadas conforme delineamento cruzado, com washout de sete dias, e as amostras sanguíneas foram coletadas no repouso, imediatamente após, 24 e 48 horas após as sessões de CO. Os marcadores dosados nas amostras foram creatinoquinase (CK), lactato desidrogenase (LDH), aspartato aminotransferase (AST), mioglobina (Mb), lactato (Lac), proteína C reativa (PCR) e haptoglobina (Hp). Em todos os níveis do CO, a CK teve um aumento significativo após 24 horas e o Lac, a LDH e a Mb no momento imediatamente após o CO. Já a AST teve aumento significativo nos níveis 2, 3 e 4, com pico de concentração após 24 horas. Os níveis séricos de PCR aumentaram apenas no momento 24 horas do nível 4 e a Hp após 48 horas do nível 3 do CO. O presente estudo demonstrou que o CO foi capaz de alterar os marcadores indiretos de dano muscular. Todavia, após 48 horas de repouso, os marcadores indiretos de dano muscular apresentaram redução, indicando um processo de recuperação. Apesar das elevações nos marcadores musculares indicadores de dano, a ausência de alterações conclusivas nos níveis séricos das proteínas inflamatórias de fase aguda sugere que o CO pode não ter uma duração ou intensidade suficiente para induzir uma resposta inflamatória sistêmica substancial
The Brazilian Army (EB) recently developed a military physical training method called Cross Operational (CO), which contains combined aerobic and resistance exercises at moderate / high intensity. The moderate / high intensity character of CO can cause impairment of muscle fibers, increasing risk of injury and exacerbation of an acute inflammatory response. In this context, analysis of indirect markers of muscle damage can be used to assess the level of intensity of CO and post-exercise recovery. The aim of this study was to observe the acute effect of CO on indirect markers of muscle damage in military personnel of EB. Twenty-four volunteers, military, male, 20,8 ± 1,8 years old participated in this study. The four sessions corresponding to the CO levels were performed according to a crossover design, with a seven-day washout and the blood samples were collected at rest, after 24 hours and 48 hours after CO sessions. The markers measured in the samples were creatinekinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), myoglobin (Mb), lactate (Lac), C-reactive protein (PCR) and haptoglobin (Hp). At all levels of CO, CK had a significant increase after 24 hours and Lac, LDH and Mb increased at the moment immediately after CO. AST had a significant increase in levels 2, 3 and 4 and a peak of concentration after 24 hours. The PCR levels increased only at the 24-hour moment after level 4 and Hp after 48 hours of level 3 of CO. This study demonstrates that CO was able to change the indirect markers of muscle damage. However, after 48 hours of rest, indirect markers of muscle damage were reduced, indicating a recovery process. Despite the elevations in muscle markers indicating damage, the absence of conclusive changes in the levels of the acute phase inflammatory proteins suggests that CO may not have sufficient duration or intensity to induce a substantial systemic inflammatory response
Subject(s)
Exercise/physiology , Macrophage Inflammatory Proteins摘要
Hypoxic-ischemic brain damage (HIBD) is referred to a common type of cerebral damage, which is caused by injury, leading to shallow bleeding in the cortex with intact cerebral pia mater. In recent years, studies show that a various kinds of immune cells and immune cellular factors are involved in the occurrence of HIBD. CC chemokine receptor 2 (CCR2) is a representative of CC chemokine receptor, and is widely distributed in cerebral neuron, astrocyte, and microglial cells, and is the main chemo-tactic factor receptor in brain tissue. CC chemokine ligand 2 (CCL2) is a kind of basophilic protein and the ligand of CCR2, and plays an important role in inflammation. In order to provide evidence for correlational studies in HIBD, this review will introduce the biological characteristics of CCR2 and CCL2, and illustrate the relationship between the immunoreactivity and HIBD.
Subject(s)
Animals , Rats , Brain Injuries/pathology , Cerebral Cortex/physiopathology , Chemokine CCL2/metabolism , Chemokines, CC/metabolism , Hypoxia-Ischemia, Brain/metabolism , Macrophage Inflammatory Proteins/metabolism , RNA, Messenger/metabolism , Rats, Sprague-Dawley , Receptors, CCR2/metabolism摘要
<p><b>UNLABELLED</b>BACKGROWND: Macrophage inflammatory protein-1α (MIP-l α/CCL3) belongs to the C-C chemokine family (CCL3), which can be secreted by macrophages, other types of hematopoietic cells and bone marrow stromal cells. Higher levels of MIP-1α were found to be associated with several kinds of hematologic malignancies, including multiple myeloma (MM), chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML). Moreover, MIP-1α has been reported to be an adverse prognostic factor for CLL. However, the impact of MIP-1α on acute myeloid leukemia (AML) has been poorly investigated.</p><p><b>OBJECTIVE</b>To investigate the influence of MIP-1α on proliferction of AML cells.</p><p><b>METHODS</b>Using MLL-AF9 induced AML mouse model, the expression of MIP-1α was measured by real time quantitative RT-PCR. AML cell proliferation was examined by cell counting and colony forming assay (CFC). The influence of blocking the MIP-1α action on the growth and pathogenic ability of AML cells was explored by using the small molecule antagonist for interfering interaction of MIP-1α with its receptor CCR1.</p><p><b>RESULTS</b>The MIP-1α could promote the proliferation and colony formation of AML cells, the blocking MIP-1a could inhibit the growth of AML cells and delay onset of AML.</p><p><b>CONCLUSION</b>The MIP-1a promotes the occurence and progression of AML, therefore blocking the MIP-1α signal pathway may be served as a strategy to inhibit the growth of AML cells, and MIP-1α can be a potential target for treatment of AML.</p>
Subject(s)
Animals , Mice , Cell Line, Tumor , Cell Proliferation , Chemokine CCL3 , Chemokine CCL4 , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Acute , Macrophage Inflammatory Proteins , Multiple Myeloma , Receptors, CCR1摘要
OBJECTIVE@#To detect the expression level of macrophage inflammatory protein-1 (MIP-1)α, MIP-1β and monocyte chemoattractant protein-1 (MCP-1) in with psoriasis vulgaris and explore the role in the pathogenesis of psoriasis vulgaris.@*METHODS@#The level of MIP-1α, MIP-1β and MCP-1 in peripheral blood from 50 patients with psoriasis vulgaris and 50 normal controls were measured by enzyme linked immunosorbent assay. The correlation with psoriasis area and severity index (PASI) was analyzed. The level of MIP-1α, MIP-1β and MCP-1 was compared between psoriasis vulgaris patients at active stage and resting stage. And the change in MIP-1α, MIP-1β and MCP-1 before and after therapy was also observed.@*RESULTS@#The content of MIP-1α, MIP-1β and MCP-1 in patients with psoriasis vulgaris was (1342.78 ± 210.30), (175.28 ± 28.18) and (266.86 ± 32.75) ng/L, respectively, significantly higher than those in control group (P<0.05). The expression level of MIP-1α, MIP-1β and MCP-1 in peripheral blood of patients with psoriasis vulgaris was positively correlated with PASI (P<0.01). After acitretin therapy, expression level of MIP-1α, MIP-1β and MCP-1 in peripheral blood of patients with psoriasis vulgaris was significantly decreased.@*CONCLUSIONS@#Chemokine factor MIP-1α, MIP-1β and MCP-1 may be involved in the pathogenesis of psoriasis vulgaris.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Young Adult , Acitretin , Therapeutic Uses , Case-Control Studies , Chemokine CCL2 , Blood , Enzyme-Linked Immunosorbent Assay , Immunosuppressive Agents , Therapeutic Uses , Keratolytic Agents , Therapeutic Uses , Macrophage Inflammatory Proteins , Blood , Psoriasis , Blood , Drug Therapy , Epidemiology , Tacrolimus , Therapeutic Uses摘要
Vesículas de membrana (VMs) derivadas de macrófagos infectados com microorganismos intracelulares têm capacidade inflamatória. Estas vesículas podem conter antígenos do patógeno, carrear moléculas de MHC II e componentes celulares que podem atuar como PAMPs ou DAMPs induzindo resposta imune. Na infecção por Leishmania, a indução de uma resposta do tipo Th1 é crucial para promoção de proteção contra o parasito. O objetivo do trabalho foi avaliar a capacidade imunomoduladora de VMs derivadas de macrófagos infectados com L. amazonensis sobre a produção de citocinas por outros macrófagos. VMs foram visualizadas por microscopia eletrônica tanto em preparações celulares como no precipitado obtido por sucessivas centrifugações de sobrenadantes de cultivos celulares. Foi observada por citometria de fluxo a presença de marcadores celulares específicos (F4/80 e CD11b) nas VMs, bem como MHC II. O tratamento de macrófagos não infectados com VMs derivadas de macrófagos infectados com L. amazonensis ocasionou aumento consistente da produção de IL-12p70 e IL-1β. Estas vesículas poderiam, portanto, favorecer a modulação da resposta imune em favor do combate ao parasito.
Membrane vesicles (MV) derived macrophages infected with intracellular microbes are proinflammatory. These vesicles contain antigens of the pathogen, carry MHC II molecules and cellular components that can act as PAMPs or DAMPs inducing immune responses. In Leishmania infection the induction of a Th1 response is crucial for the protection against the parasite. The aim of the study was to evaluate whether vesicles derived from macrophages infected with L. amazonensis had the capacity to modulate the response of other macrophages. MV were visualized by electron microscopy in cellular preparations as well in the precipitate obtained by centrifugation of cell supernatants. Flow cytometry revealed the presence of specific cellular markers (F4/80 and CD11b) in the MV, as well as MHC II. Treatment of noninfected macrophages with MV derived from L. amazonensis-infected macrophages consistently caused increased production of IL-12p70 and IL-1β. These vesicles can favor the modulation of the immune response in favor of combating the parasite.
Subject(s)
Animals , Cytokines/analysis , Leishmania/immunology , Leishmania/parasitology , Leishmania/pathogenicity , Macrophage Inflammatory Proteins , Macrophage Inflammatory Proteins/analysis , Macrophage Inflammatory Proteins/immunology , Macrophage Inflammatory Proteins/chemical synthesis , Vesicular Transport Proteins摘要
Nystatin, a polyene antifungal antibiotic, is a cholesterol sequestering agent. The antifungal agent alters composition of the plasma membrane of eukaryotic cells, whereas its effects on cells are poorly investigated. In the current study, we investigated the question of whether nystatin was able to induce expression of macrophage inflammatory protein-1 (MIP-1). THP-1 cells rarely express MIP-1alpha and MIP-1beta, however, upon exposure to nystatin, significantly elevated expression of MIP-1alpha and MIP-1beta was observed in a dose-dependent fashion at the messenger and protein levels. Cellular factors activated by nystatin as well as involved in nystatin-induced expression of MIP-1 proteins were identified in order to understand the molecular mechanisms of action of the anti-fungal agent. Treatment with nystatin resulted in enhanced phosphorylation of Akt, ERK, p38 MAPK, and JNK. Abrogation or significant attenuation of nystatin-induced expression of MIP-1alpha and MIP-1beta was observed by treatment with Akt inhibitor IV, LY294002, and SP6001250. Inhibition of ERK or p38MAPK using U0126 and SB202190 did not lead to attenuation of MIP-1 expression. In addition, inhibitors of protein kinase C, such as GF109203X and Ro-318220, also attenuated expression of MIP-1. These results indicate that nystatin is able to activate multiple cellular kinases and, among them, Akt and JNK play primary roles in nystatin-induced expression of MIP-1 proteins.
Subject(s)
Cell Membrane , Chemokine CCL3 , Chemokine CCL4 , Cholesterol , Eukaryotic Cells , Macrophage Inflammatory Proteins , Macrophages , Nystatin , p38 Mitogen-Activated Protein Kinases , Phosphorylation , Phosphotransferases , Protein Kinase C摘要
Escherichia coli enteroinvasora (EIEC) é um dos agentes etiológicos da disenteria bacilar. Seu processo fisiopatológico é desencadeado pela expressão de fatores de virulência, que proporcionam sua invasão e sobrevivência nas células do hospedeiro, ativando o sistema imune inato e adaptativo da mucosa intestinal. Trabalhos recentes têm salientado a importância do sistema de secreção e da flagelina bacteriana como agonista de receptores da imuninade inata dos macrófagos, em especial alguns dos receptores do tipo NLR. Uma vez que esta espécie de E. coli também é capaz de expressar flagelina e fazer a montagem completa do flagelo e do sistema de secreção do tipo III, a nossa proposta foi avaliar o papel da flagelina e do sistema de secreção de EIEC na resposta imune dos macrófagos murinos. Para isso, utilizamos três cepas de EIEC: a cepa selvagem; a cepa mutante no gene responsável pela síntese da flagelina; e a cepa sem o plasmídio de virulência plnv, deficiente no sistema de secreção, para a infecção de macrófagos peritoniais de camundongos C57BI/6, caspase-1-/-, IPAF-/- e ASC-/-. Neste estudo foi possível observar que o escape bacteriano e a morte dos macrófagos infectados por EIEC, assim como a ativação da caspase-1 e posterior secreção de IL-1ß é independente da flagelina bacteriana, mas dependente do sistema de secreção, além disso, a ativação da caspase-1 de macrófagos infectados por EIEC é dependente do receptor IPAF e parcialmente da proteína adaptadora ASC. Assim, no nosso modelo, a ativação da caspase-1 dos macrófagos infectados por EIEC parece estar envolvida com o processamento e secreção de IL-1ß e, possivelmente na secreção de IL-18, mas não na morte celular. No modelo de infecção in vivo, o sistema de secreção bacteriano foi importante para a sobrevivência bacteriana no hospedeiro, assim como para a indução de uma resposta inflamatória no local da infecção. Ainda, a caspase-1 parece ter um papel importante para o controle da infecção in vivo por EIEC, podendo assim contribuir para uma resposta imune protetora do hospedeiro
Enteroinvasive Escherichia coli (EIEC) is one of the etiologic agents responsible for bacillary dysentery. The pathophysiological process induced by this bacteria is triggered by the expression of virulence factors that provide the invasion and survival in host cells, resulting in activation of innate and adaptive immune system present on intestinal mucosa. Recent studies have emphasized the importance of the secretion system and bacterial flagellin as agonist of innate immune receptors present in macrophage, especially NLR (Nod like receptors). Then, our proposal was evaluate the role of flagellin (f1iC) and secretion system of EIEC in the induction of immune response of murine macrophages using the EIEC strains wild type (WT), mutant flagellin gene (f1iC), and a strain deficient in secretion system (DSS) for infection of peritoneal macrophages of C57Bl/6, caspase-1-/-, IPAF-/- and ASC-/-- mice. In this study we observed that the bacterial escape and death of infected macrophages with EIEC, the caspase-1 activation and subsequent IL-1ß secretion is independent of bacterial flagellin, but dependent of secretion system, moreover, the caspase-1 activation in infected macrophages is IPAF-dependent and partially dependent of the adapter protein ASC. Thus, in our model, the caspase-1 activation in EIEC infected macrophages seems to be involved with the processing and secretion of IL-1ß and possibly with the secretion of IL-18, but not involved with cell death. In the infection model in vivo, bacterial secretion system was important for bacterial survival in the host, as well as for the inflammatory response induction at the infection site. In addition, caspase-1 seems to have an important role to the control of in vivo infection by EIEC and can contribute to a protective immune response of the host
Subject(s)
Macrophage Inflammatory Proteins/agonists , Escherichia coli/pathogenicity , Flagellin , Flagellin/therapeutic use , Macrophage Activation/drug effects , Diarrhea , Pyroptosis , Inflammation , Macrophages/pathology摘要
BACKGROUND: Outer inflammatory protein A (OipA) is an outer membrane protein of Helicobacter pylori that is involved in inducing IL-8 and intracellular signaling. In this study, we have predicted exposure amino acid sequences of OipA for insertion in permissive sites of CstH subunit of Eschierchia coli CS3 pilli for bacterial surface display. MATERIALS AND METHODS: Databases: National Center for Biotechnology Institute and Protein Data Bank. Servers: PHD, SABLE, GOR 4, SignalP3.0, TBBpred, PRODIV-TMHMM, TMRPres2D, CPH Models, PHYRE, GETAREA, VADAR, Pep state and pep window. Software: Swiss PDB viewer and Discovery studio. RESULTS: In silico prediction of exposure amino acid sequences of OipA led to detection of six sequences of amino acid, 76-87, 106-112, 170-182, 222-230, 242-258, and 278-290. These sequences inserted between amino acid sequences 66-67, 100-101, and 109-110 of CstH that were predicted by Eskandari et al. as permissive sites of CstH. CONCLUSION: OipA has the ability to induce IL-8 from gastric epithelial cells and some papers are mentioned that this outer membrane protein involve to attachment and intracellular signaling. Receptor of OipA and adhesion motifs on this protein is unknown. Detection of exposure motifs aids to recognition of adhesion motifs and receptor of OipA on gastric epithelial cells. In this study, we have predicted exposure amino acid sequences for insert to subunit CstH of CS3 pilli E. coli for surface display.
Subject(s)
Amino Acid Sequence/analysis , Bacterial Outer Membrane Proteins/analysis , Computer Simulation/methods , Escherichia coli/physiology , Epithelial Cells/microbiology , Helicobacter pylori/physiology , Intracellular Signaling Peptides and Proteins/analysis , Macrophage Inflammatory Proteins/analysis , Stomach/cytology , User-Computer Interface摘要
To explain biological function of protein CCL15 in HCC cell lines. The different expression level of CCL15 among HCC cell lines was validated by RT-PCR and Western blot. The expression recombinant plasmid of siRNA-CCL15 was constructed successfully and transfected into high metastasis cell lines HCCML3 to observe the alteration of biological function of HCCML3. The overexpression of CCL15 in high metastasis HCC cell lines was confirmed by validation tests. After transfected with siRNA-CCL15, the average amounts of invaded cells in cell invasion assay were 657.9 (HCCML3) and 148.4(HCCML3-siCCL15) (t=19.34, P less than 0.05). And in the scratch assay, the migrating distance were (0.35+/-0.02) mm (HCCML3) and (0.82+/-0.03)mm (HCCML3-siCCL15) (t=15.67, P less than 0.05). The expression of MMP-9 in HCCML3 was higher than HCCML3-siCCL15 through Western blot. Some biological properties (migration, invasion, MMP-9) of HCCML3 transfected with siRNA-CCL15 were decreased. The results suggest CCL15 might play an important role in HCC cell invasion and metastasis through two paths of MMPs regulation and invasion potential strengthening.
Subject(s)
Humans , Carcinoma, Hepatocellular , Metabolism , Pathology , Cell Line, Tumor , Cell Movement , Cell Proliferation , Chemokines, CC , Metabolism , Liver Neoplasms , Metabolism , Pathology , Macrophage Inflammatory Proteins , Metabolism , Matrix Metalloproteinase 9 , Metabolism , Neoplasm Invasiveness , Transfection摘要
Chemokines and chemokine receptors play a role in migration of circulating leukocytes to the region of inflammation. Human LZIP is an uncharacterized transcription factor and is known to participate in leukotactin (Lkn)-1/CCL15-induced cell migration. We investigated the role of human LZIP in expression of CC chemokine receptors (CCRs) and its involvement in monocyte migration. RNase protection analysis showed that LZIP increased mRNA expression of CCR2 and CCR1 in THP-1 cells. Surface expressions of both CCR2 and CCR1 were also increased by LZIP. Results from an electrophoretic mobility shift assay showed that LZIP binds to the C/EBP element in the CCR2 promoter. LZIP also enhanced the chemotactic activities of monocyte chemoattractant protein-1/CCL2 and Lkn-1. These results suggest that LZIP regulates expression of chemokine receptors that are involved in monocyte migration.
Subject(s)
Humans , Atherosclerosis/drug therapy , CCAAT-Enhancer-Binding Proteins/genetics , Cell Line, Tumor , Cell Movement/drug effects , Chemokine CCL2/pharmacology , Chemokines, CC/pharmacology , Macrophage Inflammatory Proteins/pharmacology , Monocytes/drug effects , Promoter Regions, Genetic , Protein Binding , RNA, Messenger/analysis , Receptors, CCR1/biosynthesis , Receptors, CCR2/biosynthesis , Transcriptional Activation/drug effects , Transfection , Transgenes摘要
Chromoblastomycosis (CR) is a subcutaneous chronic mycosis characterized by a granulomatous inflammatory response. However, little is known regarding the pattern of leukocyte subsets in CR and the pathways involved in their recruitment. The objective of this study was to assess the cellular subsets, chemokine, chemokine receptors and enzymes in CR. The inflammatory infiltrate was characterized by immunohistochemistry using antibodies against macrophages (CD68), Langerhans'cells (S100), lymphocytes (CD3, CD4, CD8, CD45RO, CD20 and CD56) and neutrophils (CD15). The expression of MIP-1alpha (Macrophage inflammatory protein-1alpha), chemokine receptors (CXCR3 and CCR1) and enzymes (superoxide dismutase-SOD and nitric oxide synthase-iNOS) was also evaluated by the same method. We observed an increase in all populations evaluated when compared with the controls. Numbers of CD15+ and CD56+ were significantly lower than CD3+, CD4+, CD20+ and CD68+ cells. Statistical analysis revealed an association of fungi numbers with CD3, CD45RO and iNOS-positive cells. Furthermore, MIP-1alpha expression was associated with CD45RO, CD68, iNOS and CXCR3. Our results suggest a possible role of MIP-1alpha and fungi persistence in the cell infiltration in CR sites.
A cromomicose é micose subcutânea crônica sistêmica caracterizada por resposta inflamatória crônica granulomatosa. No entanto, existem poucos dados a respeito do padrão de subtipos de leucócitos na cromomicose e sobre as vias envolvidas no recrutamento destas células. O objetivo deste trabalho foi avaliar os tipos celulares, bem como a expressão de quimiocinas, receptores de quimiocinas e enzimas em lesões de cromomicose. O infiltrado inflamatório foi caracterizado por meio de técnica imuno-histoquímica utilizando os seguintes marcadores CD68 (macrófagos), S100 (células de Langerhans), CD3, CD4, CD8, CD45RO, CD20 e CD56 (linfócitos) e CD15 (neutrófilos). A expressão de MIP-1alfa (Proteína Inflamatória do Macrófago-1alfa), receptores de quimiocinas (CXCR3 e CCR1) e enzimas (superóxido dismutase-SOD e óxido nítrico sintase induzida-iNOS) foi avaliada pelo mesmo método. Observou-se um aumento de todas as populações celulares avaliadas em relação às amostras controle. As populações de células CD15+ e CD56+ foram significativamente menores que células CD3+, CD4+, CD20+ e CD68+. A análise estatística revelou uma correlação positiva entre o número de fungos com as células CD3, CD45RO e iNOS-positivas. A expressão de MIP-1alfa foi também associada às populações de células CD45RO, CD68, iNOS e CXCR3 positivas. Nossos resultados apontam para um possível papel de MIP-1alfa e da persistência fúngica na infiltração de células inflamatórias nos sítios de cromomicose.
Subject(s)
Humans , Middle Aged , Chromoblastomycosis/immunology , Macrophage Inflammatory Proteins , Receptors, Chemokine/immunology , Biomarkers , Blood Cell Count , Case-Control Studies , Chromoblastomycosis/enzymology , Immunity, Cellular , Immunohistochemistry , Langerhans Cells/immunology , Lymphocytes/immunology , Macrophages/immunology , Neutrophils/immunology , Nitric Oxide Synthase/immunology , Superoxide Dismutase/immunology摘要
OBJECTIVE@#To detect the expressions of chemokines interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 (MIP-1) mRNA in non-small cell lung cancer (NSCLC) tissues, to analyze their relationship with microvessel counts (MVC), and their significance in clinic pathologic features of NSCLC.@*METHODS@#In situ hybridization was used to measure the expressions of chemokine IL-8, MCP-1, and MIP-1 mRNA in 40 NSCLC tissues and 10 normal pulmonary tissues, and immunohistochemical staining was carried out to measure the MVC in the above tissues.@*RESULTS@#The positive ratios of IL-8, MCP-1, and MIP-1 mRNA in the 40 NSCLC tissues were apparently higher than those in the 10 normal contrast tissues and the difference was statistically significant. The numbers varied accordingly with the different clinic pathologic features of NSCLC, showing that Group T(3) > Group T(2) or Group T(1), Group III stage> Group II stage> Group I stage Group lymph node and remote transferred > Group non-transferred, and Group of survival time no more than 3 years > Group of survival time more than 3 years. The positive expressions among IL-8, MCP-1,and MIP-1 mRNA and between these and the MVC all had mutually positive correlation.@*CONCLUSION@#Chemokine IL-8, MIP-1, and MIP-1 in NSCLC tissues might cooperate with one another to promote the tumor angiogenesis and affect the progression, metastasis and prognosis of the tumor.
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Carcinoma, Non-Small-Cell Lung , Metabolism , Chemokine CCL2 , Metabolism , Interleukin-8 , Metabolism , Lung Neoplasms , Metabolism , Macrophage Inflammatory Proteins , Metabolism , Neovascularization, Pathologic , Prognosis摘要
O objetivo do presente estudo foi avaliar os níveis das metaloproteinases da matriz MMP-9, MMP-3 e MMP-13, e das quimiocinas MCP-1, MIP-1β e RANTES, no fluido gengival de dentes sob força ortodôntica. Foram recrutados 14 pacientes (3 homens e 11 mulheres) que foram submetidos à movimentação ortodôntica dos caninos superiores. Amostras do fluido gengival foram coletadas com tiras de Periopaper em diferentes tempos. O volume do FG foi determinado com o uso do Periotron® e os niveis das MMPs e das quimiocinas quantificados usando-se uma multianálise imunoenzimática com microesferas. Os resultados mostraram que existe um aumento significativo no volume do FG na área de pressão em quase todos os tempos analisados, quando comparados às áreas de tensão. Os níveis da MMP-9 foram muito superiores aos das MMP-13 e MMP-3. Na análise da evolução do tempo pode ser observada uma alteração significativa nos níveis da quantidade total de MMP-9, MMP-13 e MMP-3 e na concentração de MMP-13 e MMP-3 durante o período de movimentação dentária no lado de pressão. A elevação dos níveis de expressão destas MMPs 1 hora após a aplicação da força ortodôntica sugere que estas enzimas estejam envolvidas na remodelação periodontal induzida. As quimiocinas MCP-1, MIP-1β e RANTES foram detectadas no sulco gengival em todos os diferentes intervalos de tempo analisados, nas áreas de tensão e de pressão. Porém, diversas amostras estavam abaixo do nível de detecção do ensaio e, os níveis dessas quimiocinas no fluido gengival não parecem ser alterados pelas forças ortodônticas.
The goal of the present study was to evaluate the levels of the matrix metalloproteinases MMP-9, MMP-3 and MMP-13 and of the chemokines MCP-1, MIP-1β and RANTES in the gingival crevicular fluid of teeth under orthodontic forces. Fourteen subjects (3 males and 11 females) were enrolled and subjected to orthodontic tooth movement of their maxillary canines. Samples of gingival crevicular fluid were collected from both tension and pressure sides using Periopaper strips at different time points. The volume of GCF was determined using a Periotron® and the levels of MMPs and chemokines quantified using a multiplex microbead immunoassay. The results demonstrated that the levels of MMP-9 were higher than the levels of MMP-13 and MMP-3. Statistically significant fluctuations during the orthodontic tooth movement could be detected for the total amount of MMP-9, MMP-13 and MMP-3 and for the concentration of MMP-13 and MMP-3 at the pressure side. The elevation in the levels of these MMPs, 1 hour after the application of the orthodontic force, suggests that these enzymes are involved in the induced periodontal remodeling. The chemokines MCP-1, MIP-1β and RANTES were detected in the GCF in both tension and pressure sides at different time points. However, several samples were below the level of detection of the assay and the levels of theses mediators in GCF did not seem to be altered by the orthodontic forces.
Subject(s)
Humans , Cytokines , Macrophage Inflammatory Proteins , Matrix Metalloproteinase 9 , Monocyte Chemoattractant Proteins , Tooth Movement Techniques/adverse effects , Orthodontics, Corrective/methods , Cuspid , Gingival Crevicular Fluid/chemistry , Environmental Monitoring , Data Interpretation, Statistical摘要
A amostragem é um dos procedimentos básicos indispensáveis ao manejo integrado de pragas. Neste experimento, comparou-se a capacidade de coleta de dois métodos de amostragem da lagarta-da-soja (Anticarsia gemmatalis Hueb., 1818) e do percevejo-verde-pequeno (Piezodorus guildinii Westw., 1837) na cultura da soja semeada em três espaçamentos entre linhas (0,30; 0,40 e 0,50m). Foi utilizado o delineamento inteiramente casualizado, com dez repetições (amostragens), em esquema fatorial 2x3; utilizaram-se dois métodos de amostragem (pano-de-batida e pano-vertical) e três espaçamentos entre linhas. A população de lagarta-da-soja e de percevejo-verde-pequeno foi avaliada nos estádios V8 e R6, respectivamente. Para lagartas, os resultados indicam maior eficiência do pano-vertical em relação pano-de-batida. Nos menores espaçamentos, o pano-vertical não deixou clara sua maior capacidade de coleta de percevejos, como observado para lagartas. Estes resultados demonstram que são necessárias pesquisas visando a aprofundar a avaliação dos métodos de amostragens de pragas da soja cultivada em diferentes espaçamentos.
Subject(s)
Cimicidae , Macrophage Inflammatory Proteins , Pest Control摘要
OBJECTIVE@#investigate and compare the effect of valsartan and indapamide on inflammatory cytokines in hypertension.@*METHODS@#Forty-one untreated patients with mild to moderate hypertension and 20 age and sex-matched normotensives were enrolled in this study. Hypertensives were treated with indapamide 1.5 mg/d (n=20) or valsartan 80 mg/d (n=21) for 4 weeks, and blood samples for determining monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1alpha), sP-selectin, asymmetric dimethylarginin (ADMA), angiotensin II (Ang II), and 6-keto-PGF1alpha were collected before the treatment and 4 weeks after the treatment.@*RESULTS@#Hypertensives exhibited significantly higher blood pressure, as well as elevated plasma levels of MCP-1, MIP-1alpha, sP-selectin and serum level of ADMA compared with the normotensives. Nevertheless, there was no significant difference in serum 6-keto-PGF1alpha and Ang II between the hypertensives and the normotensives. After the treatment with indapamide or valsartan for 4 weeks, both the systolic and diastolic blood pressures, though still higher than those of the normotensives, decreased markedly. After the treatment with indapamide for 4 weeks, MCP-1, MIP-1alpha and sP-selectin slightly decreased, but not statistically significant (P>0.05). Those cytokines decreased significantly after being treated with valsartan for 4 weeks [(19.16+/-3.11) pg/mL vs (16.08+/-2.67) pg/mL, P0.05).@*CONCLUSION@#The levels of MCP-1, MIP-1alpha, sP-selectin and ADMA were elevated in mild to moderate hypertensives. Valsartan and indapamide have similar blood pressure lowering effect. Valasartan exerts more significant effect on cytokines than indapamide does.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Angiotensin II Type 1 Receptor Blockers , Therapeutic Uses , Antihypertensive Agents , Therapeutic Uses , Chemokine CCL2 , Blood , Chemokine CCL3 , Chemokine CCL4 , Cytokines , Blood , Diuretics , Therapeutic Uses , Hypertension , Blood , Drug Therapy , Indapamide , Therapeutic Uses , Macrophage Inflammatory Proteins , Blood , P-Selectin , Blood , Tetrazoles , Therapeutic Uses , Valine , Therapeutic Uses , Valsartan摘要
This study was aimed to explore the expression of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 in bcr/abl fusion gene positive CML cells, and to study the effects of P210(bcr/abl) fusion protein tyrosine kinase on expression of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNAs in chronic myeloid leukemia cells. The expression levels of MIP-1alpha, MCP-1 and their receptors CCR-1, CCR-2 mRNA were detected by semi-quantitative RT-PCR in bcr/abl negative cells, bcr/abl positive cells, and P210(bcr/abl)-Rb-C-Box positive cells. The results showed that MIP-1alpha and CCR-1 mRNAs were expressed in bcr/abl negative cells, but not in positive cells. Both MCP-1 and CCR-2 mRNA cannot be detected in both bcr/abl positive and negative cells. After inhibiting P210(bcr/abl) tyrosine kinase activity by Rb-C-Box, expressions of MIP-1alpha and CCR-1 mRNAs were restored to normal (similar to P210(bcr/abl) negative cells). It is concluded that P210(bcr/abl) fusion protein inhibits the expression of MIP-1alpha and CCR-1 in chronic myeloid leukemia cells, but does not inhibit MCP-1 and CCR-2 mRNA expressions in these leukemia cells.
Subject(s)
Humans , Chemokine CCL2 , Genetics , Chemokine CCL3 , Chemokine CCL4 , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Metabolism , Macrophage Inflammatory Proteins , Genetics , Receptors, CCR1 , Receptors, CCR2 , Receptors, Chemokine , Genetics , Tumor Cells, Cultured摘要
HIV patients are predisposed to the development of hypertriglyceridemia and hypercholesterolemia as a result of both viral infection and HIV infection therapy, especially the protease inhibitors. Chemokines and cytokines are present at sites of inflammation and can influence the nature of the inflammatory response in atherosclerosis. We investigated the correlation between biochemical variables and beta-chemokines (MIP-1alpha and RANTES) and the apolipoprotein E genotype in HIV-infected individuals. The apolipoproteins were measured by nephelometry. Triglycerides and total cholesterol were determined by standard enzymatic procedures. The beta-chemokines were detected by ELISA. The genetic category of CCR5 and apolipoprotein E were determined by PCR amplification and restriction enzymes. Immunological and virological profiles were assessed by TCD4+ and TCD8+ lymphocyte counts and viral load quantification. Positive correlations were found between apo E and CD8+ (p = 0.035), apo E and viral load (p = 0.018), MIP-1alpha and triglycerides (p = 0.039) and MIP-1a and VLDL (p = 0.040). Negative correlations were found between viral load and CD4+ (p = 0.05) and RANTES and CD4+ (p = 0.029). The beta-chemokine levels may influence lipid metabolism in HIV-infected individuals.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Apolipoproteins E/blood , Chemokine CCL5 , HIV Infections/blood , Lipoproteins/blood , Macrophage Inflammatory Proteins , Apolipoproteins E/genetics , Apolipoproteins E/metabolism , Biomarkers/blood , Chemokine CCL5 , Enzyme-Linked Immunosorbent Assay , Genotype , HIV Infections/metabolism , Lipoproteins/metabolism , Macrophage Inflammatory Proteins , Nephelometry and Turbidimetry , Polymerase Chain Reaction , /blood , Viral Load摘要
PURPOSE: The pathologic mechanisms of central nervous system(CNS) injuries in human meningitis are not yet completely understood. Recent studies indicate that the host inflammatory responses are as important in brain damage as the infecting organisms and toxins. There have been some reports on the relationship of nitric oxide(NO), macrophage inflammatory protein-1 alpha (MIP-1 alpha ), and lactoferrin in bacterial meningitis, but few reports in aseptic meningitis. Thus, we investigated the concentrations of NO, MIP-1 alpha and lactoferrin in cerebrospinal fluid(CSF) and serum of patients with aseptic meningitis and control subjects and evaluated their relationship with other parameters of meningitis. METHODS: CSF and blood were obtained from 25 subjects with aseptic meningitis and 15 control subjects. After centrifugation, supernatants were stored at -70degrees C and we assayed the concentrations of NO, MIP-1 alpha and lactoferrin with the ELISA method. There were no patients with neurologic sequelae after being recovered from aseptic meningitis. RESULTS: Concentrations of CSF and serum NO, MIP-1 alpha were not increased in aseptic meningitis subjects compared to control subjects. Concentration of CSF lactoferrin was significantly elevated in patients with aseptic meningitis and concentration of serum lactoferrin was significantly decreased in patients with aseptic meningitis compared with those in control subjects(P<0.05). CSF lactoferrin level was positively correlated with CSF WBC counts(rs=0.449, P=0.007), especially with neutrophil counts(rs=0.574, P<0.001) and CSF protein level(rs=0.508, P=0.002). CONCLUSION: Lactoferrin plays an important role in aseptic meningitis and may be released from neutrophils recruited from blood to the CSF through breakdown of blood-brain barrier. NO and MIP-1 alpha may not be important factors in the pathogenesis of aseptic meningitis without neurologic sequelae.
Subject(s)
Humans , Blood-Brain Barrier , Brain , Centrifugation , Enzyme-Linked Immunosorbent Assay , Lactoferrin , Macrophage Inflammatory Proteins , Macrophages , Meningitis , Meningitis, Aseptic , Meningitis, Bacterial , Neutrophils , Nitric Oxide摘要
OBJECTIVE@#To explore the microvessel counts and the expressions of interleukin-8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), and macrophage inflammatory protein-1 ( MIP-1) alpha mRNA in the pathological scar tissues.@*METHODS@#Immunohistochemical method of avidin-biotin complex was used for microvessel counts on the routinely formalin-fixed and paraffin-embedded sections of specimens of hypertrophic scars, keloids, normal skin, and surgical scar, and in situ hybridization for the expressions of IL-8, MCP-1, MIP-1alpha mRNA.@*RESULTS@#The microvessel counts as well as the positive rates and the scorings of IL-8, MCP-1, and MIP-1alpha mRNA were significantly higher in pathological scars than those in the normal skin and surgical scar (all P < 0.05). The microvessel counts were significantly higher in the positive cases of IL-8, MCP-1 and MIP-1alpha mRNA than those in the negative ones (P < 0.05). The close positive correlations were found among the microvessel counts and the expressive scorings of 3 factors (P < 0.05). The close positive correlations were also found among the expressive scorings of IL-8, MCP-1, and MIP-1alpha mRNA in pathological scars. Microvessel counts were significantly higher in hypertrophic scars with the course less than 1 year than those with the course more than 1 year.@*CONCLUSION@#IL-8, MCP-1 and MIP-1alpha play important roles in promoting the neovascularization of pathological scars.