Establishment of rat model of silicotuberculosis and its pathological characteristic

Dong, Hongyan; Wu, Jing; Yabo, Yang; Yang, Xiaolin; Wan, Wang; Mu, Min; Wenyang, Wang; Chen, Zhaoquan; Xing, Yanwei; Zhang, Rongbo

doi:10.1179/2047773214y.0000000157

Cited by 8 publications

(7 citation statements)

References 9 publications

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“…Silica particles increase intracellular replication of Mycobacterium tuberculosis and release from macrophages [24] . In rat models, defence against Mycobacterium tuberculosis becomes poorer as silicosis progresses [25] . However, silica-induced Th1 responses, with TNF-alpha and IFN-gamma production, should contribute to resistance to, or elimination of, Mycobacterium tuberculosis [26] .…”

Section: Pathophysiologymentioning

confidence: 99%

Mini-review: Silico-tuberculosis

Lanzafame

Vento

2021

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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Silicosis continues to be a serious health issue in many countries and its elimination by 2030 (a target set by WHO and the International Labour Organization in 1995) is virtually impossible. The risk to develop pulmonary tuberculosis for silicosis patients is higher than for non-silicosis people, and there is also an increased risk of both pulmonary and extrapulmonary tuberculosis in individuals exposed to silica. HIV coinfection adds further to the risk, and in some countries, such as South Africa, miners living with HIV are a considerable number. The diagnosis of active tuberculosis superimposed on silicosis is often problematic, especially in initial phases, and chest X-ray and smear examination are particularly important for the diagnosis of pulmonary tuberculosis. Treatment is difficult; directly observed therapy is recommended, a duration of at least eight months is probably needed, drug reactions are frequent and the risk of relapse higher than in non-silicosis patients. TB prevention in silicosis patients is essential and include active surveillance of the workers, periodic chest X-rays, tuberculin skin test or interferon-gamma releasing assay testing, and, importantly, adoption of measures to reduce the exposure to silica dust. Chemoprophylaxis is possible with different regimens and needs to be expanded around the world, but efficacy is unfortunately limited. Silico-tuberculosis is still a challenging health problem in many countries and deserves attention worldwide.

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Section: Pathophysiologymentioning

confidence: 99%

Mini-review: Silico-tuberculosis

Lanzafame

Vento

2021

Journal of Clinical Tuberculosis and Other Mycobacterial Diseas

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“…Many animal models are used to study M.tb lesions including mice, guinea pigs, rabbits, non-human primates, bovine calves, zebrafish, rats, ferrets, mini pigs, fruit flies, nematodes, planarians, and even amoebas [ 43 – 56 ]. Due to the small size, cost-efficiency, and availability of reagents, mice are widely used and have been crucial for determining immunological requirements that restrict M.tb growth [ 57 , 58 ].…”

Section: Genetic Variation In Mice Controls Necrotizing Responses To mentioning

confidence: 99%

Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies

2015

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A key aspect of TB pathogenesis that maintains Mycobacterium tuberculosis in the human population is the ability to cause necrosis in pulmonary lesions. As co-evolution shaped M. tuberculosis (M.tb) and human responses, the complete TB disease profile and lesion manifestation are not fully reproduced by any animal model. However, animal models are absolutely critical to understand how infection with virulent M.tb generates outcomes necessary for the pathogen transmission and evolutionary success. In humans, a wide spectrum of TB outcomes has been recognized based on clinical and epidemiological data. In mice, there is clear genetic basis for susceptibility. Although the spectra of human and mouse TB do not completely overlap, comparison of human TB with mouse lesions across genetically diverse strains firmly establishes points of convergence. By embracing the genetic heterogeneity of the mouse population, we gain tremendous advantage in the quest for suitable in vivo models. Below, we review genetically defined mouse models that recapitulate a key element of M.tb pathogenesis—induction of necrotic TB lesions in the lungs—and discuss how these models may reflect TB stratification and pathogenesis in humans. The approach ensures that roles that mouse models play in basic and translational TB research will continue to increase allowing researchers to address fundamental questions of TB pathogenesis and bacterial physiology in vivo using this well-defined, reproducible, and cost-efficient system. Combination of the new generation mouse models with advanced imaging technologies will also allow rapid and inexpensive assessment of experimental vaccines and therapies prior to testing in larger animals and clinical trials.

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“…This system is a non-invasive instrument that allows animal inhalation of silica particles and may be set to a certain dust concentration. Compared with intratracheal administration of silica dust ( 20 , 21 ), using the dynamic pollution control system facilitated the establishment of an ideal silicosis model. Histopathological observations demonstrated that, following inhalation of SiO 2 for 4 weeks, silicotic nodules containing macrophages developed in the lung tissues of rats.…”

Section: Discussionmentioning

confidence: 99%

Influence of the interaction between Ac‑SDKP and Ang II on the pathogenesis and development of silicotic fibrosis

et al. 2018

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N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural tetrapeptide that is released from thymosin β4 by prolyl oligopeptides. It is hydrolyzed by the key enzyme of the renin-angiotensin system, angiotensin-converting enzyme (ACE). The aim of the present study was to investigate the alterations in Ac-SDKP and the ACE/angiotensin II (Ang II)/angiotensin II type 1 (AT1) receptor axis and its impact on the pathogenesis and development of silicotic fibrosis. For in vivo studies, a HOPE MED 8050 exposure control apparatus was used to establish different stages of silicosis in a rat model treated with Ac-SDKP. For in vitro studies, cultured primary lung fibroblasts were induced to differentiate into myofibroblasts by Ang II, and were pretreated with Ac-SDKP and valsartan. The results of the present study revealed that, during silicosis development, ACE/Ang II/AT1 expression in local lung tissues increased, whereas that of Ac-SDKP decreased. Ac-SDKP and the ACE/AT1/Ang II axis were inversely altered in the development of silicotic fibrosis. Ac-SDKP treatment had an anti-fibrotic effect in vivo. Compared with the silicosis group, the expression of α-smooth muscle actin (α-SMA), Collagen (Col) I, Fibronectin (Fn) and AT1 were significantly downregulated, whereas matrix metalloproteinase-1 (MMP-1) expression and the MMP-1/tissue inhibitor of metalloproteinases-1 (TIMP-1) ratio was increased in the Ac-SDKP treatment group. In vitro, pre-treatment with Ac-SDKP or valsartan attenuated the expression of α-SMA, Col I, Fn and AT1 in Ang II-induced fibroblasts. In addition, MMP-1 expression and the MMP-1/TIMP-1 ratio were significantly higher in Ac-SDKP and valsartan pre-treatment groups compared with the Ang II group. In conclusion, the results of the present study suggest that an imbalance between Ac-SDKP and ACE/Ang II/AT1 molecules promotes the development of silicosis and that Ac-SDKP protects against silicotic fibrosis by inhibiting Ang II-induced myofibroblast differentiation and extracellular matrix production.

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Establishment of rat model of silicotuberculosis and its pathological characteristic

Cited by 8 publications

References 9 publications

Mini-review: Silico-tuberculosis

Mini-review: Silico-tuberculosis

Mouse models of human TB pathology: roles in the analysis of necrosis and the development of host-directed therapies

Influence of the interaction between Ac‑SDKP and Ang II on the pathogenesis and development of silicotic fibrosis

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