Lung fibrosis induced by crystalline silica particles is uncoupled from lung inflammation in NMRI mice

Rabolli, Virginie; Re, Sandra Lo; Uwambayinema, Francine; Yakoub, Yousof; Lison, Dominique; Huaux, François

doi:10.1016/j.toxlet.2011.03.009

Cited by 46 publications

(47 citation statements)

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“…In addition, the number of inflammatory cells in BALF, the LT content and the mRNA levels of cytokines were not affected by the 2-week treatment; thus, pranlukast treatment has no effect on the acute inflammatory response. Interestingly, recent evidence has demonstrated that inflammation might not play a pivotal role in the pathogenesis of human IPF or in silica-induced pulmonary fibrosis in mice [1,15,16]. Although further detailed pharmacological studies are necessary to determine whether the acute inflammatory response affects the progression of pulmonary fibrosis in the chronic phase of the disease, our results show that pranlukast treatment has antifibrotic effects that are independent of the effect on this response.…”

Section: Discussionmentioning

confidence: 57%

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Shimbori

Shiota²,

Okunishi³

2012

Int Arch Allergy Immunol

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Background: Although cysteinyl leukotrienes (CysLTs) have been implicated in the etiology of acute inflammatory diseases, recent studies have suggested that they also directly stimulate fibroblasts. However, their precise role in the pathogenesis of pulmonary fibrosis is unclear. Methods: In this study, we evaluated the effect of both short- and long-term treatment with pranlukast, a CysLT type 1 (CysLT₁) receptor antagonist, on silica-induced pulmonary fibrosis in mice, which is characterized by persistent progression of fibrosis in the chronic phase. Pranlukast (30 mg/kg/day) was administered orally to mice for 2 or 10 weeks after intratracheal silica instillation. Results: Pranlukast treatment for 10 weeks significantly attenuated the progression of pulmonary fibrosis, and decreased the content of CysLTs and LTB₄, which were markedly increased in the bronchoalveolar lavage fluid (BALF) and lung tissues of silica-instilled mice in the chronic phase. However, pranlukast treatment for 2 weeks neither affected the acute inflammatory response induced by silica instillation nor inhibited the onset of fibrosis. The expression of TGF-β1 and TNF-α was not affected by pranlukast treatment for either 2 or 10 weeks. Conclusions: Pranlukast attenuates the progression of pulmonary fibrosis in the chronic phase but has no effect on the acute inflammatory response or on the onset of pulmonary fibrosis. The antifibrotic effect of pranlukast may be exhibited by antagonizing the direct profibrotic effect of CysLTs, without affecting the expression of other profibrotic cytokines such as TGF-β1 and TNF-α, and also by decreasing the production of CysLTs and LTB₄.

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Section: Discussionmentioning

confidence: 57%

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Shimbori

Shiota²,

Okunishi³

2012

Int Arch Allergy Immunol

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“…Similarly, type I interferons are necessary in the establishment of silica-induced lung inflammation while they are not necessary for lung fibrosis [42]. Finally, different treatments with anti-inflammatory molecules reduced lung inflammation without modifying collagen deposition in animals [51], [52]. Conventional anti-inflammatory agents do not alter silicosis and final outcome in patients and there is no evidence that corticosteroid or prednisolone confer significant benefits for patients with chronic or accelerated silicosis [1], [53].…”

Section: Discussionmentioning

confidence: 99%

Uncoupling between Inflammatory and Fibrotic Responses to Silica: Evidence from MyD88 Knockout Mice

Yakoub

Devosse

et al. 2014

PLoS ONE

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The exact implication of innate immunity in granuloma formation and irreversible lung fibrosis remains to be determined. In this study, we examined the lung inflammatory and fibrotic responses to silica in MyD88-knockout (KO) mice. In comparison to wild-type (WT) mice, we found that MyD88-KO animals developed attenuated lung inflammation, neutrophil accumulation and IL-1β release in response to silica. Granuloma formation was also less pronounced in MyD88-KO mice after silica. This limited inflammatory response was not accompanied by a concomitant attenuation of lung collagen accumulation after silica. Histological analyses revealed that while pulmonary fibrosis was localized in granulomas in WT animals, it was diffusely distributed throughout the parenchyma in MyD88-KO mice. Robust collagen accumulation was also observed in mice KO for several other components of innate immunity (IL-1R, IL-1, ASC, NALP3, IL-18R, IL-33R, TRIF, and TLR2-3-4,). We additionally show that pulmonary fibrosis in MyD88-KO mice was associated with the accumulation of pro-fibrotic regulatory T lymphocytes (T regs) and pro-fibrotic cytokine expression (TGF-β, IL-10 and PDGF-B), not with T helper (Th) 17 cell influx. Our findings indicate that the activation of MyD88-related innate immunity is central in the establishment of particle-induced lung inflammatory and granuloma responses. The development of lung fibrosis appears uncoupled from inflammation and may be orchestrated by a T reg-associated pathway.

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“…RNA Extraction and Quantification-Total RNA extraction and quantification by quantitative PCR were performed as described previously (17). Sequences of interest were amplified by PCR using the following forward primers (Invitrogen): CGG CTA CCA CAT CCA AGC AA (mouse 18 S RNA), GAC GGA CCC CAA AAG ATG AAG (mouse IL-1␤), CCA GCC AGA GTG GAA CTT TCG (mouse NLRP3), GGA GCT CAC AAT GAC TGT GCT TA (mouse ASC), GGA CTT CTC AAG ATC ATG GCT ACT T (mouse CXCR2), GAC TGC GAC TTC CTG GAG GAT (mouse ngp) and reverse primers: ATA CGC TAT TGG AGC TGG ATT ACC (mouse 18s RNA), CTC TTC GTT GAT GTG CTG CTG TG (mouse IL-1␤), TAC AAA TGG AGA TGC GGG AGA (mouse NLRP3), CTG CCA CAG CTC CAG ACT CTT(mouse ASC), TAG TAG AGG TGT TTG CTG AAG ACG A (mouse CXCR2), and GTA TCC TCT CGA CTG CAA TCC CTG (mouse ngp).…”

Section: Methodsmentioning

confidence: 99%

Critical Role of Aquaporins in Interleukin 1β (IL-1β)-induced Inflammation

Rabolli

Wallemme

et al. 2014

Journal of Biological Chemistry

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Background: Aquaporins are channels permeable to water, and they are essential for immune cell migration. Results: We demonstrate that aquaporin-mediated water fluxes are necessary for the NLRP3 inflammasome-dependent release of mature IL-1␤ in vitro and in vivo. Conclusion: Aquaporins are implicated in the mechanisms of proinflammatory cytokine secretion during inflammation. Significance: The discovery of a new function for AQPs opens new diagnostic and therapeutic opportunities in inflammatory disorders.

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Lung fibrosis induced by crystalline silica particles is uncoupled from lung inflammation in NMRI mice

Cited by 46 publications

References 50 publications

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Pranlukast, a Cysteinyl Leukotriene Type 1 Receptor Antagonist, Attenuates the Progression but Not the Onset of Silica-Induced Pulmonary Fibrosis in Mice

Uncoupling between Inflammatory and Fibrotic Responses to Silica: Evidence from MyD88 Knockout Mice

Critical Role of Aquaporins in Interleukin 1β (IL-1β)-induced Inflammation

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