Regulation of lung fibroblast proliferation and protein synthesis by bronchiolar lavage in experimental silicosis

Benson, Stephen C.; Belton, John C.; Scheve, Larry G.

doi:10.1016/s0013-9351(86)80168-2

Cited by 29 publications

(11 citation statements)

References 30 publications

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“…This is associated with an inflammatory cell responses characterized by alveolitis with recruitment of inflammatory cells, particularly neutrophils, and may result in pulmonary fibrosis and impaired lung function 13 . IT of quartz into rats produces inflammatory reactions followed by histological changes characteristic of lung fibrosis 14 , similar to human conditions. With a dose of 2 mg/rat IT, fine particles of quartz caused toxicity with severe inflammatory changes characterized by neutrophil infiltration and edema after 28 days 6 .…”

Section: Introductionmentioning

confidence: 74%

Immunohistochemical Characteristics of Surfactant Proteins A, B, C and D in Inflammatory and Tumorigenic Lung Lesions of F344 Rats

et al. 2014

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Surfactant proteins (SPs), originally known as human lung surfactants, are essential to respiratory structure and function. There are 4 subtypes, SP-A, SP-B, SP-C and SP-D, with SP-A and SP-D having immunological functions, and SP-B and SP-C having physicochemical properties that reduce the surface tension at biological interfaces. In this experiment, the expressions of SP-A, SP-B, SP-C and SP-D in lung neoplastic lesions induced by N-bis (2-hydroxypropyl) nitrosamine (DHPN) and inflammatory lesions due to quartz instillation were examined and compared immunohistochemically. Formalin fixed paraffin embedded (FFPE) lung samples featuring inflammation were obtained with a rat quartz instillation model, and neoplastic lesions, hyperplasias and adenomas, were obtained with the rat DHPN-induced lung carcinogenesis model. In the rat quartz instillation model, male 10-week old F344 rats were exposed by intratracheal instillation (IT) to quartz at a dose of 2 mg/rat suspended in saline (0.2 ml) on day 0, and sacrificed on day 28. Lung tumorigenesis in F344 male rats was initiated by DHPN in drinking water for 2 weeks, and the animals were then sacrificed in week 30. Lung proliferative lesions, hyperplasias and adenomas, were observed with DHPN, and inflammation was observed with quartz. The expressions of SP-A, SP-B, SP-C and SP-D were examined immunohistochemically. SP-B and SP-C showed strong expression in lung hyperplasias and adenomas, while SP-A and SP-D were observed in mucus or exudates in inflammatory alveoli. These results suggest the possibility that SP-B and SP-C are related to lung tumorigenesis.

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Section: Introductionmentioning

confidence: 74%

Immunohistochemical Characteristics of Surfactant Proteins A, B, C and D in Inflammatory and Tumorigenic Lung Lesions of F344 Rats

et al. 2014

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“…This is associated with inflammatory cell responses characterized by alveolitis with recruitment of inflammatory cells, particularly neutrophils, and may result in pulmonary fibrosis and impaired lung function 15 . Intratracheal instillation of quartz into rats produces inflammatory reactions followed by histological changes characteristic of lung fibrosis 16 , similar to pathological changes in humans. At a dose of 2 mg/rat i.t., fine particles of quartz caused severe inflammatory changes in the lung characterized by neutrophil infiltration and edema after 28 days 10 .…”

Section: Introductionmentioning

confidence: 76%

Suppressive effects of the expectorant drug ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats

et al. 2017

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Surfactant proteins (SPs) are essential to respiratory structure and function. The expectorant drug ambroxol hydrochloride is clinically prescribed to stimulate pulmonary surfactant and airway serous secretion. Therefore, ambroxol hydrochloride may affect SP production and pulmonary inflammation. Lung toxicity of fine particles of various materials has been examined previously in our in vivo bioassay using the intratracheal (i.t.) instillation approach. In the present study, we evaluated modulatory effects of ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats. Male 6-week-old F344 rats were exposed by i.t. instillation to 2 mg of quartz particles suspended in 0.2 mL of saline. Ambroxol hydrochloride was administered at 0, 12, and 120 ppm in rat basal diet for 28 days, and then formalin-fixed paraffin-embedded lung, liver, and kidney samples were prepared. No changes in general condition, body and organ weights, or food consumption upon exposure to quartz were noted. The mean ambroxol intake in rats of the 12 ppm group was comparable to the human conventional dose. Histopathology of lung lesions was evaluated, and the degree of inflammation was scored. At 120 ppm, ambroxol hydrochloride significantly decreased individual lung inflammation scores for pulmonary edema and lymph follicle proliferation around the bronchiole, as well as the total inflammation score, in quartz-treated rats. Expression of SP-C in the type II alveolar cells and macrophages was greater in inflammatory lesions than in non-inflamed areas. Ambroxol treatment did not affect expression of SP-B and SP-C. In conclusion, we demonstrated that ambroxol hydrochloride relieves quartz-induced lung inflammation.

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“…Silicosis is a disorder that is characterized by abnormalities in collagen synthesis and deposition within the lung [56, 57]. The pathogenesis of silicosis, for which there is still no effective clinical therapy, remains unknown.…”

Section: Discussionmentioning

confidence: 99%

Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy

et al. 2016

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BackgroundSilicosis is characterized by accumulation of fibroblasts and excessive deposition of extracellular matrix. Monocyte chemotactic protein-1-induced protein 1 (MCPIP1) plays a critical role in fibrosis induced by SiO2. However, the details of the downstream events of MCPIP1 activity in pulmonary fibrosis remain unclear. To elucidate the role of MCPIP1-induced autophagy in SiO2-induced fibrosis, both the upstream molecular mechanisms and the functional effects of SiO2 on cell apoptosis, proliferation and migration were investigated.ResultsExperiments using primary cultures of alveolar macrophages from healthy donors and silicosis patients as well as differentiated U937 macrophages demonstrated the following results: 1) SiO2 induced macrophage autophagy in association with enhanced expression of MCPIP1; 2) autophagy promoted apoptosis and activation of macrophages exposed to SiO2, and these events induced the development of silicosis; 3) MCPIP1 facilitated macrophage apoptosis and activation via p53 signaling-mediated autophagy; and 4) SiO2-activated macrophages promoted the proliferation and migration of fibroblasts via the MCPIP1/p53-mediated autophagy pathway.ConclusionsOur results elucidated a link between SiO2-induced fibrosis and MCPIP1/p53 signaling-mediated autophagy. These findings provide novel insight into the potential targeting of MCPIP1 or autophagy in the development of potential therapeutic strategies for silicosis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12989-016-0167-z) contains supplementary material, which is available to authorized users.

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Regulation of lung fibroblast proliferation and protein synthesis by bronchiolar lavage in experimental silicosis

Cited by 29 publications

References 30 publications

Immunohistochemical Characteristics of Surfactant Proteins A, B, C and D in Inflammatory and Tumorigenic Lung Lesions of F344 Rats

Immunohistochemical Characteristics of Surfactant Proteins A, B, C and D in Inflammatory and Tumorigenic Lung Lesions of F344 Rats

Suppressive effects of the expectorant drug ambroxol hydrochloride on quartz-induced lung inflammation in F344 rats

Macrophage-derived MCPIP1 mediates silica-induced pulmonary fibrosis via autophagy

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