scholarly journals Effect of Liuweibuqi capsules on the balance between MMP-9 and TIMP1 and viability of alveolar macrophages in COPD

2017 ◽  
Vol 37 (5) ◽  
Author(s):  
Chengyang Wang ◽  
Huanzhang Ding ◽  
Xiao Tang ◽  
Zegeng Li ◽  
Lei Gan
Keyword(s):  
Lung Function ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Alveolar Macrophages ◽  
Serum Levels ◽  
Chronic Obstructive ◽  
High Dose ◽  
Group Model ◽  
Tnf Α ◽  
Model Control

The present study aims to investigate the effect of Liuweibuqi (LWBQ) capsules on the expression of matrix metalloproteinase (MMP)-9 and TIMP1 and cell viability of alveolar macrophages (AMs) in chronic obstructive pulmonary disease (COPD). Rats were randomly divided into normal control (NC) group, model control (MC) group, Jinshuibao (JSB) group, spleen aminopeptidase (PAT) group, and low dose of LWBQ (LWBQ low), mid dose of LWBQ (LWBQ mid), and high dose of LWBQ (LWBQ high) group (n=10). Lung function was measured with a spirometer. Serum cytokines including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were detected using ELISA. The expressions of MMP-9 and TIMP1 were detected by quantitative real-time PCR (qRT-PCR) and Western blot. MTT assay and flow cytometry were used to measure cell viability and apoptosis. Compared with the NC group, body weight and lung function were reduced in the MC group. In addition, the serum levels of IL-6 and TNF-α were higher in the MC group than those in the NC group. The expression of MMP-9 protein in the AMs from rats was higher, and TIMP1 protein was lower in the MC group compared with the NC group. After LWBQ capsules treatment, compared with the MC group, the expression of inflammatory cytokines and MMP-9 were lower and TIMP1 was higher. Moreover, after LWBQ-medicated serum treatment, the release of inflammatory cytokines was reduced from AMs. Besides, LWBQ-medicated serum decreased the expression of MMP-9 and increased the expression of TIMP1 and cell viability compared with those in MC group. In conclusion, LWBQ capsules can inhibit the release of inflammatory cytokines, promote cell viability in AMs, and regulate the expression of MMP-9 and TIMP1.

scholarly journals Effect of Liuweibuqi Capsules in Pulmonary Alveolar Epithelial Cells and COPD Through JAK/STAT Pathway

2017 ◽  
Vol 43 (2) ◽  
pp. 743-756 ◽  
Author(s):  
Chengyang Wang ◽  
Huanzhang Ding ◽  
Xiao Tang ◽  
Zegeng Li ◽  
Lei Gan
Keyword(s):  
Lung Function ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Transforming Growth Factor ◽  
Interferon Γ ◽  
Normal Group ◽  
Alveolar Epithelial Cells ◽  
Chronic Obstructive ◽  
Model Control ◽  
Stat Pathway

Background/Aims: To evaluate the effect of Liuweibuqi capsules on chronic obstructive pulmonary disease (COPD) through the JAK/STAT pathway. Methods: Lung function was measured with a spirometer. Changes in lung histology were observed using H&E staining. Cigarette smoke extract combined with lipopolysaccharide (CSE+LPS) was used to establish the cellular COPD model. Cytokine levels were determined using ELISA, and changes in the JAK/STAT pathway were evaluated using western blotting. The CCK8 method and flow cytometry were used to measure cell viability and apoptosis, respectively. Results: Liuweibuqi capsules reduced the damage in the lung tissues and the loss of lung function in the COPD rats. Additionally, the levels of interleukin (IL)-1β, interferon γ (IFNγ), IL-6, tumor necrosis factor (TNF)-α and transforming growth factor (TGF)-β1 were higher, whereas IL-10 was lower in the model control (MC) and CSE+LPS groups than in the normal group. The phosphorylation levels of JAK1, JAK2, STAT1, STAT3 and STAT5 were higher and the levels of SOCS1 and SOCS3 were lower in the MC group and CSE+LPS group compared with the normal group. After Liuweibuqi capsule treatment, the expression of inflammatory cytokines and elements of the JAK/STAT pathway were lower. In addition, over-expression of STAT3 blocked the effects of the Liuweibuqi capsules on the release of inflammatory cytokines, cell viability and apoptosis. Conclusion: Our findings suggested that Liuweibuqi capsule might effectively ameliorate the progression of COPD via the JAK/STAT pathway.

scholarly journals Serum CYR61 Is Associated With Airway Inflammation and Is a Potential Biomarker for Severity in Chronic Obstructive Pulmonary Disease

2021 ◽  
Vol 8 ◽  
Author(s):  
Zhu-Xia Tan ◽  
Lin Fu ◽  
Wen-Jing Wang ◽  
Ping Zhan ◽  
Hui Zhao ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Pulmonary Disease ◽  
Inflammatory Cytokines ◽  
Pulmonary Inflammation ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Copd Patients ◽  
Tnf Α ◽  
High Level

Background: Cysteine-rich 61 (CYR61) and inflammation was upregulated in the lungs of patients with chronic obstructive pulmonary disease (COPD). However, the association between CYR61 and inflammation was unclear in COPD patients. This study aimed to analyze the association of serum CYR61 with pulmonary inflammation and lung function indexes in COPD patients.Methods: One hundred and fifty COPD patients and 150 control subjects were enrolled. Serum and pulmonary CYR61 was detected. Lung function indexes were evaluated in COPD patients.Results: Serum CYR61 level was elevated and pulmonary CYR61 expression was upregulated in COPD patients. An increased CYR61 was associated with decreased pulmonary function indexes in COPD patients. Further analyses showed that nuclear factor-kappa B (NF-κB) p65-positive nuclei was elevated in the lungs of COPD patients with high level of CYR61. Accordingly, serum monocyte chemotactic protein (MCP)-1 and tumor necrosis factor α (TNF-α), two downstream inflammatory cytokines of NF-κB pathway, were increased in parallel with CYR61, among which serum MCP-1 and TNF-α were the highest in COPD patients with high level of CYR61. Moreover, a positive correlation, determined by multivariate regression that excluded the influence of age, gender and smoking, was observed between serum CYR61 and inflammatory cytokines in COPD patients.Conclusion: These results provide evidence that an increased CYR61 is associated with pulmonary inflammation and COPD progression. Inflammatory cytokines may be the mediators between CYR61 elevation and COPD progression.

scholarly journals Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Dexun Hao ◽  
Yanshuang Li ◽  
Jiang Shi ◽  
Junguang Jiang
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Lung Function ◽  
Cell Viability ◽  
Pulmonary Disease ◽  
Cigarette Smoke ◽  
Inflammatory Cell ◽  
Inflammatory Cell Infiltration ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Tnf Α

Abstract Background Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction and progressive lung inflammation. As the primary ingredient of a traditional Chinese medical herb, Baicalin has been previously shown to possess anti-inflammatory abilities. Thus, the current study aimed to elucidate the mechanism by which baicalin alleviates COPD. Methods Baicalin was adopted to treat cigarette smoke in extract-exposed MLE-12 cells after which cell viability and apoptosis were determined. The production of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8 were determined by enzyme-linked immunoassay. A COPD mouse model was constructed via exposure to cigarette smoke and lipopolysaccharide, baicalin treatment. Lung function and inflammatory cell infiltration were determined and the production of Muc5AC, TNF-α, IL-6, IL-8 in the bronchoalveolar lavage fluid (BALF) was assayed by ELISA. The effect of HSP72 and JNK on COPD following treatment with baicalin was assessed both in vivo and in vitro by conducting loss- and gain- function experiments. Results Baicalin improved lung function evidenced by reduction in inflammatory cell infiltration and Muc5AC, TNF-α, IL-6 and IL-8 levels observed in BALF in mice. Baicalin was further observed to elevate cell viability while inhibited apoptosis and TNF-α, IL-6 and IL-8 levels in MLE-12 cells. Baicalin treatment increased HSP72 expression, while its depletion reversed the effect of baicalin on COPD. HSP72 inhibited the activation of JNK, while JNK activation was found to inhibit the effect of baicalin on COPD. Conclusions Baicalin upregulated the expression of HSP72, resulting in the inhibition of JNK signaling activation, which ultimately alleviates COPD.

scholarly journals Effects of Shugan-Jianpi Recipe on the Expression of the p38 MAPK/NF-κB Signaling Pathway in the Hepatocytes of NAFLD Rats

Medicines ◽  
2018 ◽  
Vol 5 (3) ◽  
pp. 106 ◽  
Author(s):  
Yuanjun Deng ◽  
Kairui Tang ◽  
Runsen Chen ◽  
Yajie Liu ◽  
Huan Nie ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Low Dose ◽  
Serum Levels ◽  
Inflammatory Factors ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Dose ◽  
Model Group ◽  
Necrosis Factor Alpha ◽  
Tnf Α

Background: In traditional Chinese medicine, the Shugan-Jianpi recipe is often used in the treatment of nonalcoholic fatty liver disease (NAFLD). This study aimed to explore the mechanism of the Shugan-Jianpi recipe in relation to rats with NAFLD induced by a high-fat diet. Methods: Rats were randomly divided into eight groups: normal group (NG), model group (MG), low-dose Chaihu–Shugan–San group (L-CG), high-dose Chaihu–Shugan–San group (H-CG), low-dose Shenling–Baizhu–San group (L-SG), high-dose Shenling–Baizhu–San group (H-SG), low dose of integrated-recipes group (L-IG), and high dose of integrated-recipes group (H-IG). After 26 weeks, a lipid profile, aspartate, and alanine aminotransferases in serum were detected. The serum levels of inflammatory factors including interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha (TNF-α) were analyzed using the enzyme linked immunosorbent assay (ELISA) method. Hepatic pathological changes were observed with hematoxylin-eosin (HE) and oil red O staining. The expression of the p38 mitogen-activated protein kinases (MAPK)/nuclear factor-κB (NF-κB) pathway was detected by quantitative real-time PCR and Western blotting. Results: A pathological section revealed that NAFLD rats have been successfully reproduced. Compared with the model group, each treatment group had different degrees of improvement. The Shugan-Jianpi recipe can inhibit the serum levels of IL-1β, IL-6, and TNF-α in NAFLD rats. The expression of mRNA and a protein related to the p38 MAPK/NF-κB signaling pathway were markedly decreased as a result of the Shugan-Jianpi recipe. Conclusions: The Shugan-Jianpi recipe could attenuate NAFLD progression, and its mechanism may be related to the suppression of the p38 MAPK/NF-κB signaling pathway in hepatocytes.

Lipidomics Study of the Therapeutic Mechanism of Plantaginis Semen in Potassium Oxonate-Induced Hyperuricemia Rat

2020 ◽  
Author(s):  
Wenjun Shi ◽  
Fei Yang ◽  
Liting Wang ◽  
Nankun Qin ◽  
Chengxiang Wang ◽  
...  
Keyword(s):  
Male Rats ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
High Dose ◽  
Intragastric Administration ◽  
Group Model ◽  
Model Group ◽  
Tnf Α ◽  
Plantaginis Semen ◽  
Potassium Oxonate

Abstract BackgroundPlantaginis semen has been widely used as folk medicine and health care food against hyperuricemia (HUA) and gout, but little was known about its pharmacological mechanism. MethodsThe model was established by potassium oxonate intragastric administration. 42 Sprague-Dawley (SD) male rats were randomly divided into the control group, model group, benzbromarone group (10 mg/kg) and three Plantaginis semen groups (n = 7). The Plantaginis semen groups were treated orally with Plantaginis semen at 0.9375, 1.875 and 3.75 g/kg for 28 days. The levels of serum uric acid (UA), creatinine (Cr), triacylglycerol (TG) and tumor necrosis factor-α (TNF-α) were detected using enzyme-linked immunosorbent assay kits. Ultra performance liquid chromatography quadrupole time of flight mass spectrometry (UPLC-Q-TOF/MS) was used as the basis for serum lipidomics analysis, and orthogonal partial least squares discriminant analysis (OPLS-DA) was carried out for the pattern recognition and characteristic metabolites identification. The relative levels of critical regulatory factors of urate anion transporter 1(URAT1) and phosphatidylinositol 3-kinase/ protein kinases B (PI3K/Akt) were determined by quantitative real-time polymerase chain reaction (RT-qPCR). ResultsCompared with the model group, the levels of serum UA, Cr, and TG were significantly (p<0.01) decreased in benzbromarone and three Plantaginis semen groups and the level of serum TNF-α was significantly (p<0.05) decreased in benzbromarone and low dose of Plantaginis semen group. With lipidomics analysis, significant lipid metabolic perturbations were observed in HUA rats, 13 metabolites were identified as potential biomarkers and glycerophospholipid metabolism pathway was mostly affected. These perturbations can be partially restored via treatment of benzbromarone and Plantaginis semen. Additionally, the URAT1 and PI3K/Akt mRNA expression levels were significantly decreased (p<0.05) after treatment with benzbromarone and high dose of Plantaginis semen. ConclusionsPlantaginis semen had significant anti-HUA, anti-inflammatory and renal protection effects and could attenuate potassium oxonate-induced HUA through regulation of lipid metabolism disorder. Trial registrationNot applicable

scholarly journals Synergistic Effects of Acidic pH and Pro-Inflammatory Cytokines IL-1β and TNF-α for Cell-Based Intervertebral Disc Regeneration

2020 ◽  
Vol 10 (24) ◽  
pp. 9009
Author(s):  
Chiara Borrelli ◽  
Conor T. Buckley
Keyword(s):  
Intervertebral Disc ◽  
Cell Viability ◽  
Inflammatory Cytokines ◽  
Cell Function ◽  
Synergistic Effects ◽  
Dominant Factor ◽  
Disc Regeneration ◽  
Tnf Α ◽  
Intervertebral Disc Regeneration ◽  
Pro Inflammatory Cytokines

The intervertebral disc (IVD) relies mainly on diffusion through the cartilaginous endplates (CEP) to regulate the nutrient and metabolites exchange, thus creating a challenging microenvironment. Degeneration of the IVD is associated with intradiscal acidification and elevated levels of pro-inflammatory cytokines. However, the synergistic impact of these microenvironmental factors for cell-based therapies remains to be elucidated. The aim of this study was to investigate the effects of low pH and physiological levels of interleukin-1ß (IL-1β) and tumour necrosis factor-α (TNF-α) on nasal chondrocytes (NCs) and subsequently compare their matrix forming capacity to nucleus pulposus (NP) cells in acidic and inflamed culture conditions. NCs and NP cells were cultured in low glucose and low oxygen at different pH conditions (pH 7.1, 6.8 and 6.5) and supplemented with physiological levels of IL-1β and TNF-α. Results showed that acidosis played a pivotal role in influencing cell viability and matrix accumulation, while inflammatory cytokine supplementation had a minor impact. This study demonstrates that intradiscal pH is a dominant factor in determining cell viability and subsequent cell function when compared to physiologically relevant inflammatory conditions. Moreover, we found that NCs allowed for improved cell viability and more effective NP-like matrix synthesis compared to NP cells, and therefore may represent an alternative and appropriate cell choice for disc regeneration.

scholarly journals Functional, inflammatory and interstitial impairment due to artificial stone dust ultrafine particles exposure

2019 ◽  
Vol 76 (12) ◽  
pp. 875-879 ◽  
Author(s):  
Noa Ophir ◽  
Amir Bar Shai ◽  
Rafi Korenstein ◽  
Mordechai R Kramer ◽  
Elizabeth Fireman
Keyword(s):  
Inflammatory Cytokines ◽  
Ultrafine Particles ◽  
Forced Expiratory Volume ◽  
Raw Material ◽  
High Dose ◽  
Necrosis Factor Alpha ◽  
Single Breath ◽  
Stone Dust ◽  
Tnf Α ◽  
Artificial Stone

ObjectiveArtificial stone dust (ASD) contains high levels of ultrafine particles (UFP <1 µm) which penetrate deeply into the lungs. This study aimed to demonstrate the direct effect of UFP in the lungs of ASD-exposed workers on functional inflammatory and imaging parameters.Methods68 workers with up to 20 years of ASD exposure at the workplace were recruited from small enterprises throughout the country and compared with 48 non-exposed individuals. Pulmonary function test (PFT), CT, induced sputum (IS) and cytokine analyses were performed by conventional methods. The CT scans were evaluated for features indicative of silicosis in three zones of each lung. UFP were quantitated by the NanoSight LM20 system (NanoSight, Salisbury) using the Nanoparticle Tracking Analysis. Interleukin (IL)-6, IL-8 and tumour necrosis factor alpha (TNF-α) levels were measured by Luminex (R&D Systems).ResultsThirty-four patients had CT scores between 0 and 42, and 29 of them were diagnosed with silicosis. Content of the UFP retrieved from IS supernatants correlated negatively with the PFT results (total lung capacity r=−0.347, p=0.011; forced expiratory volume in 1 s r=−0.299, p=0.046; diffusion lung carbon monoxide in a single breath r=−0.425, p=0.004) and with the CT score (r=0.378, p=0.023), and with the inflammatory cytokines IL-8 (r=0.336, p=0.024), IL-6 (r=0.294, p=0.065) and TNF-α (r=0.409, p=0.007). Raw material of ASD was left to sedimentate in water for <15 min, and 50% of the floating particles were UFP. A cut-off of 8×106 UFP/mL in IS samples had a sensitivity of 77% to predict pulmonary disease.ConclusionsThis is the first demonstration of an association between UFP-related decreased PFT results, worsening of CT findings and elevation of inflammatory cytokines, which may be attributed to high-dose inhalation of UFP of ASD at the workplace.

scholarly journals Impact of Matrix Metalloproteinase 9 on COPD Development in Polish Patients: Genetic Polymorphism, Protein Level, and Their Relationship with Lung Function

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Iwona Gilowska ◽  
Łukasz Kasper ◽  
Katarzyna Bogacz ◽  
Jan Szczegielniak ◽  
Teresa Szymasek ◽  
...  
Keyword(s):  
Genetic Polymorphism ◽  
Lung Function ◽  
Copy Number Variants ◽  
Serum Levels ◽  
Chronic Obstructive ◽  
Healthy Individuals ◽  
Tissue Destruction ◽  
Genotype Frequencies ◽  
Gene Copies ◽  
Copd Patients

Chronic obstructive pulmonary disease (COPD) is characterized by a decline of lung function and symptoms such as chronic bronchitis and emphysema leading from lung tissue destruction. Increased activity of matrix metalloproteinases (MMPs) and an imbalance between MMPs and their tissue inhibitors (TIMPs) are considered as factors influencing the pathogenesis of COPD. We investigated the role of genetic polymorphism and expression level of MMP-9 and concentration of its complexes with TIMPs in the development of COPD among Polish patients. We analyzed SNP in the promoter region of MMP-9 gene (rs3918242) using PCR-RFLP method among 335 COPD patients and 309 healthy individuals. Additionally, 60 COPD patients and 61 controls were tested for copy number variants (CNV) of MMP-9 (by quantitative real-time PCR) and serum levels of MMP-9 and its complexes with TIMP1 and TIMP2 (using ELISA). All subjects were analyzed for lung function using spirometry (FEV1% and FEV1/FVC parameters). We observed that allele and genotype frequencies of the SNP rs3918242, as well as the number of gene copies, were similar in COPD patient and controls groups. Serum levels of MMP-9 and MMP-9/TIMP1 complex were significantly higher in COPD patients in comparison to controls groups, although independently of analyzed gene polymorphisms. Additionally, the significant inverse relationships between parameters of lung function (FEV1% and FEV1/FVC) and proteins level were found in ridge regression models, especially we found that FEV1% decreased when MMP-9 level increased in controls and patients with COPD group. In conclusion, we found that COPD patients were predisposed to produce more MMP-9 and MMP-9/TIMP1 complex than healthy individuals. This phenomenon is probably associated with the disease-related lung environment but not with genetic features of the MMP-9.

Interleukin-6, Hepcidin, and Other Biomarkers in Anemia of Chronic Disease (ACD) and Chemotherapy-Induced Anemia (CIA): Potential Therapeutic Targets.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2086-2086 ◽  
Author(s):  
Saroj Vadhan-Raj ◽  
Xiao Zhou ◽  
Carlos E. Bueso-Ramos ◽  
Shreyaskumar Patel ◽  
Robert S Benjamin ◽  
...  
Keyword(s):  
Chronic Disease ◽  
Inflammatory Cytokines ◽  
Linear Regression Analysis ◽  
Transferrin Saturation ◽  
Serum Levels ◽  
Serum Samples ◽  
Anemia Of Chronic Disease ◽  
Baseline Serum ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

Abstract Abstract 2086 Background: Anemia in patients with malignancies can be multifactorial including anemia of chronic disease (ACD), also known as anemia of inflammation (AI), and chemotherapy (CT)-induced anemia (CIA) from myelosuppression. Although, exact mechanism for ACD is not known, induction of hepcidin, a key iron-regulatory hormone, by Interleukin (IL)-6 and other pro-inflammatory cytokines with resulting hypoferremia and limitation of iron supply to the bone marrow appear to be major contributors to pathogenesis of anemia. Hepcidin reduces iron levels by inducing degradation of the cellular iron exporter, ferroportin. The objective of this study was to examine the levels of various cytokines/regulators that may play role in ACD. Methods: Chemo-naïve patients with sarcoma scheduled to initiate first-line doxorubicin-based chemotherapy had blood samples drawn at baseline, and following chemotherapy (post cycles1, 3 and 6) for analysis of pro-inflammatory cytokines/other biomarkers of anemia. Serum samples were analyzed for IL-1β, IL-6, TNF-α, Hepcidin, hemojuvelin, ferroportin, soluble transferrin receptor (sTFR), and C-reactive protein (CRP) using ELISA techniques (R&D Diagnostics, Uscn Life Science Inc, or Abnova). Correlations between these biomarkers and Hgb levels at baseline and during the study period were calculated by linear regression analysis (SAS 9.2). Results: Of the 49 patients enrolled on to the clinical trial, there were 26 (53%) women and 23 (47%) men, with median age 45 years (range 19–65 years). Twenty-five percent of the patients had Hgb less than 12g/dL (range, 8.9–15.9 g/dL) prior to CT. At baseline, 50% of the pts had hypoferremia with low serum iron and transferrin saturation <20%. Baseline serum levels of IL-6 (r= −0.73, p<0.0001), hepcidin (r= −0.46, p=0.005), CRP (r= −0.46, p=0.003), sTFR (r= −0.32, p=0.064) inversely correlated with hemoglobin levels prior to CT, supporting their role in ACD. During CT (median 4, range; 1–6 cycles), Hgb declined in all pts with 55% requiring PRBC transfusions (77% of pts starting with baseline Hgb < 12 g/dL vs 47% of pts with baseline Hgb > 12 g/dL). Interestingly, as shown below, Hepcidin, IL-6, and sTFR all significantly negatively correlated with Hgb levels during CT. No significant correlation was found for IL-1β, TNF-α, ferroportin, or hemojuvelin levels with Hgb. Conclusions: IL-6 and Hepcidin pathway appears to play an important role in anemia in cancer patients before and during CT. Treatment with novel agents targeting this pathway may provide effective strategies for prevention and treatment of ACD and CIA. Disclosures: Vadhan-Raj: JNJ: Research Funding.

scholarly journals Virulence and Immune Response Induced by Mycobacterium avium Complex Strains in a Model of Progressive Pulmonary Tuberculosis and Subcutaneous Infection in BALB/c Mice

2013 ◽  
Vol 81 (11) ◽  
pp. 4001-4012 ◽  
Author(s):  
Mónica González-Pérez ◽  
Leonardo Mariño-Ramírez ◽  
Carlos Alberto Parra-López ◽  
Martha Isabel Murcia ◽  
Brenda Marquina ◽  
...  
Keyword(s):  
Immune Response ◽  
Pulmonary Tuberculosis ◽  
Inflammatory Cytokines ◽  
Mycobacterium Avium ◽  
High Expression ◽  
High Dose ◽  
Content Type ◽  
Subcutaneous Infection ◽  
Tnf Α ◽  
Anti Inflammatory

ABSTRACTThe genusMycobacteriumcomprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies withMycobacterium tuberculosis. The biological differentiation betweenM. tuberculosisand nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not.Mycobacterium aviumcomplex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after theM. tuberculosiscomplex. Here, we evaluated the virulence and immune response ofM. aviumsubsp.aviumandMycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.

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