BACKGROUND: Asthma is characterized by inflammation and remodeling. Mast cells are generally increased in bronchial mucosa of subjects with asthma. These cells release a wide variety of cytokines and mediators that have the capacity to stimulate other resident cells such as smooth muscle cells and fibroblasts. OBJECTIVE: This study was designed to evaluate whether mast cells modulate collagen production by bronchial fibroblasts isolated from subjects with asthma and normal subjects through cytokine production. METHODS: Human mast cells were cocultured for 72 hours with primary bronchial fibroblasts isolated from bronchial biopsies of subjects with mild asthma and normal controls. Procollagen I (alpha1), IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2 gene expression by bronchial fibroblasts and IL-4 and IL-4delta2 gene expression by mast cells were quantified by real-time RT-PCR. IL-4 production was also measured by ELISA in culture supernatants. RESULTS: Procollagen I (alpha1) gene expression by fibroblasts from subjects with asthma was significantly higher compared with cells from normal controls when cocultured with mast cells. Mast cells expressed IL-4 isoform and IL-4delta2, an alternative splice variant of IL-4. Coculture significantly increased the expression of IL-4 but not IL-4delta2 by mast cells when they were cultured with fibroblasts from subjects with asthma compared with cells from normal controls. Neutralization of IL-4 abrogated collagen mRNA expression. There was no significant change in IL-4Ralpha or IL-13Ralpha1. However, IL-13Ralpha2 gene expression was significantly reduced in fibroblasts from subjects with asthma. CONCLUSION: These results suggest that inflammatory process may regulate airway remodelling through crosstalk between inflammatory and structural cells. Targeting this crosstalk may have therapeutic application. CLINICAL IMPLICATIONS: Understanding mechanisms that govern airway remodeling and collagen deposition in asthma is a step toward therapeutic management of this disease. In this work, we found that mast cell-fibroblast crosstalk may be a potential future target to control some aspects of airway remodeling.
BACKGROUND:Asthma is characterized by inflammation and remodeling. Mast cells are generally increased in bronchial mucosa of subjects with asthma. These cells release a wide variety of cytokines and mediators that have the capacity to stimulate other resident cells such as smooth muscle cells and fibroblasts. OBJECTIVE: This study was designed to evaluate whether mast cells modulate collagen production by bronchial fibroblasts isolated from subjects with asthma and normal subjects through cytokine production. METHODS:Human mast cells were cocultured for 72 hours with primary bronchial fibroblasts isolated from bronchial biopsies of subjects with mild asthma and normal controls. Procollagen I (alpha1), IL-4Ralpha, IL-13Ralpha1, and IL-13Ralpha2 gene expression by bronchial fibroblasts and IL-4 and IL-4delta2 gene expression by mast cells were quantified by real-time RT-PCR. IL-4 production was also measured by ELISA in culture supernatants. RESULTS: Procollagen I (alpha1) gene expression by fibroblasts from subjects with asthma was significantly higher compared with cells from normal controls when cocultured with mast cells. Mast cells expressed IL-4 isoform and IL-4delta2, an alternative splice variant of IL-4. Coculture significantly increased the expression of IL-4 but not IL-4delta2 by mast cells when they were cultured with fibroblasts from subjects with asthma compared with cells from normal controls. Neutralization of IL-4 abrogated collagen mRNA expression. There was no significant change in IL-4Ralpha or IL-13Ralpha1. However, IL-13Ralpha2 gene expression was significantly reduced in fibroblasts from subjects with asthma. CONCLUSION: These results suggest that inflammatory process may regulate airway remodelling through crosstalk between inflammatory and structural cells. Targeting this crosstalk may have therapeutic application. CLINICAL IMPLICATIONS: Understanding mechanisms that govern airway remodeling and collagen deposition in asthma is a step toward therapeutic management of this disease. In this work, we found that mast cell-fibroblast crosstalk may be a potential future target to control some aspects of airway remodeling.
Authors: Irina G Luzina; Virginia Lockatell; Nevins W Todd; Achsah D Keegan; Jeffrey D Hasday; Sergei P Atamas Journal: Immunology Date: 2011-01-10 Impact factor: 7.397
Authors: Irina G Luzina; Achsah D Keegan; Nicola M Heller; Graham A W Rook; Terez Shea-Donohue; Sergei P Atamas Journal: J Leukoc Biol Date: 2012-07-10 Impact factor: 4.962
Authors: Rafael Firszt; Dave Francisco; Tony D Church; Joseph M Thomas; Jennifer L Ingram; Monica Kraft Journal: Eur Respir J Date: 2013-05-16 Impact factor: 16.671
Authors: Neerad C Mishra; Jules Rir-Sima-Ah; Raymond J Langley; Shashi P Singh; Juan C Peña-Philippides; Takeshi Koga; Seddigheh Razani-Boroujerdi; Julie Hutt; Matthew Campen; K Chul Kim; Yohannes Tesfaigzi; Mohan L Sopori Journal: J Immunol Date: 2008-06-01 Impact factor: 5.422
Authors: Omar S El Safoury; Marwa M Fawzy; Rania M Abdel Hay; Akmal S Hassan; Zeinab M El Maadawi; Laila A Rashed Journal: Indian J Dermatol Date: 2011-11 Impact factor: 1.494