Mast cells and mast cell tryptase enhance migration of human lung fibroblasts through protease-activated receptor 2

Bagher, Mariam; Larsson‐Callerfelt, Anna Karin; Rosmark, Oskar; Hällgren, Oskar; Bjermer, Leif; Westergren‐Thorsson, Gunilla

doi:10.1186/s12964-018-0269-3

Cited by 53 publications

(51 citation statements)

References 55 publications

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“…To study the effect of tryptase and chymase on fibroblast migration, tryptase (75 ng/mL) and chymase (1 ng/mL) were added to HFL-1 cells. In line with our previous data [ 19 ], tryptase significantly enhanced the migratory capacity of fibroblasts at 24 h ( p = 0.001), 48 h ( p = 0.001) and 72 h ( p = 0.001), whereas chymase did not show any significant effect on fibroblast migration ( Figure 3 a). Higher concentration of chymase (10 and 100 ng/mL) appeared to be toxic, where the cells detached from the cell culture plastic plate and migration could not be observed (data not shown).…”

Section: Resultssupporting

confidence: 93%

“…This could be due to the presence of both chymase and tryptase in LAD2 cells ([ 30 ]. We have previously shown that mast cells and tryptase enhanced the migratory capacity of fibroblasts, which was attenuated by a PAR2 antagonist, confirming that the mechanism behind the induced migration of fibroblasts involve PAR2 activation [ 19 ], as supported by other studies [ 22 ]. In the present study, tryptase enhanced fibroblast migration.…”

Section: Discussionsupporting

confidence: 73%

“…However, despite evidence that mast cells may activate fibroblasts and contribute to remodeling, the mechanism for this interaction is poorly understood. We have recently shown that mast cells and mast cell tryptase promote fibroblast migration via protease-activated receptor 2 (PAR2) [ 19 ]. To follow up on these results, we evaluated the effect of mast cells and mast cell proteases tryptase and chymase on the release of mediators from lung fibroblasts derived from healthy individuals and IPF patients.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Crosstalk between Mast Cells and Lung Fibroblasts Is Modified by Alveolar Extracellular Matrix and Influences Epithelial Migration

Bagher

Rosmark

Rendin

et al. 2021

IJMS

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Mast cells play an important role in asthma, however, the interactions between mast cells, fibroblasts and epithelial cells in idiopathic pulmonary fibrosis (IPF) are less known. The objectives were to investigate the effect of mast cells on fibroblast activity and migration of epithelial cells. Lung fibroblasts from IPF patients and healthy individuals were co-cultured with LAD2 mast cells or stimulated with the proteases tryptase and chymase. Human lung fibroblasts and mast cells were cultured on cell culture plastic plates or decellularized human lung tissue (scaffolds) to create a more physiological milieu by providing an alveolar extracellular matrix. Released mediators were analyzed and evaluated for effects on epithelial cell migration. Tryptase increased vascular endothelial growth factor (VEGF) release from fibroblasts, whereas co-culture with mast cells increased IL-6 and hepatocyte growth factor (HGF). Culture in scaffolds increased the release of VEGF compared to culture on plastic. Migration of epithelial cells was reduced by IL-6, while HGF and conditioned media from scaffold cultures promoted migration. In conclusion, mast cells and tryptase increased fibroblast release of mediators that influenced epithelial migration. These data indicate a role of mast cells and tryptase in the interplay between fibroblasts, epithelial cells and the alveolar extracellular matrix in health and lung disease.

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Section: Resultssupporting

confidence: 93%

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Crosstalk between Mast Cells and Lung Fibroblasts Is Modified by Alveolar Extracellular Matrix and Influences Epithelial Migration

Bagher

Rosmark

Rendin

et al. 2021

IJMS

Self Cite

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“…This enzyme exerts a fibrogenic activity, by triggering collagen production by the fibroblasts ( Akers et al, 2000 ; Levi-Schaffer and Piliponsky, 2003 ). Although its role, as a mediator of the fibrotic process, has been analyzed in a few studies ( Kondo et al, 2001 ; Bagher et al, 2018 ), further studies are required to increase the knowledge on its functions and to explore the possibility of using inhibitors targeting the enzyme for an antifibrotic therapeutic intervention. Furthermore, the contribution of plasminogen activator inhibitor-1 (PAI-1) to fibrosis progression through the activation of mast cells has recently emerged.…”

Section: Organ Fibrosis Emt and Possible Anti-emt Therapeutic Stratementioning

confidence: 99%

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

Gregorio

Robuffo

Spalletta³

et al. 2020

Front. Cell Dev. Biol.

102

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Fibrosis is a chronic and progressive disorder characterized by excessive deposition of extracellular matrix, which leads to scarring and loss of function of the affected organ or tissue. Indeed, the fibrotic process affects a variety of organs and tissues, with specific molecular background. However, two common hallmarks are shared: the crucial role of the transforming growth factor-beta (TGF-β) and the involvement of the inflammation process, that is essential for initiating the fibrotic degeneration. TGF-β in particular but also other cytokines regulate the most common molecular mechanism at the basis of fibrosis, the Epithelial-to-Mesenchymal Transition (EMT). EMT has been extensively studied, but not yet fully explored as a possible therapeutic target for fibrosis. A deeper understanding of the crosstalk between fibrosis and EMT may represent an opportunity for the development of a broadly effective anti-fibrotic therapy. Here we report the evidences of the relationship between EMT and multi-organ fibrosis, and the possible therapeutic approaches that may be developed by exploiting this relationship.

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“…Their location in the dermis, their ability to release vasoactive and proinflammatory substances, and the expression of IgE receptors on their surfaces imply that they have important roles in the immunity of the skin to infectious or harmful agents (132)(133)(134). Mast cells are probably involved in the mechanisms of fibroblast proliferation, blood flow control, and angiogenesis (135)(136)(137)(138)(139). These functions are implicated in extracellular matrix remodeli and in the cicatricial (scarring) and fibrotic processes associated with skin lesions (Table 1) (139).…”

Section: Basophils and Mast Cellsmentioning

confidence: 99%

Organization of the Skin Immune System and Compartmentalized Immune Responses in Infectious Diseases

Quaresma

2019

Clin Microbiol Rev

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SUMMARY The skin is an organ harboring several types of immune cells that participate in innate and adaptive immune responses. The immune system of the skin comprises both skin cells and professional immune cells that together constitute what is designated skin-associated lymphoid tissue (SALT). In this review, I extensively discuss the organization of SALT and the mechanisms involved in its responses to infectious diseases of the skin and mucosa. The nature of these SALT responses, and the cellular mediators involved, often determines the clinical course of such infections. I list and describe the components of innate immunity, such as the roles of the keratinocyte barrier and of inflammatory and natural killer cells. I also examine the mechanisms involved in adaptive immune responses, with emphasis on new cytokine profiles, and the role of cell death phenomena in host-pathogen interactions and control of the immune responses to infectious agents. Finally, I highlight the importance of studying SALT in order to better understand host-pathogen relationships involving the skin and detail future directions in the immunological investigation of this organ, especially in light of recent findings regarding the skin immune system.

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Mast cells and mast cell tryptase enhance migration of human lung fibroblasts through protease-activated receptor 2

Cited by 53 publications

References 55 publications

Crosstalk between Mast Cells and Lung Fibroblasts Is Modified by Alveolar Extracellular Matrix and Influences Epithelial Migration

Crosstalk between Mast Cells and Lung Fibroblasts Is Modified by Alveolar Extracellular Matrix and Influences Epithelial Migration

The Epithelial-to-Mesenchymal Transition as a Possible Therapeutic Target in Fibrotic Disorders

Organization of the Skin Immune System and Compartmentalized Immune Responses in Infectious Diseases

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