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Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice

BACKGROUND: Asthma leads to structural changes in the airways, including the modification of extracellular matrix proteins such as tenascin-C. The role of tenascin-C is unclear, but it might act as an early initiator of airway wall remodelling, as its expression is increased in the mouse and human a...

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Autores principales: Meuronen, Anna, Karisola, Piia, Leino, Marina, Savinko, Terhi, Sirola, Kristiina, Majuri, Marja-Leena, Piirilä, Päivi, Virtanen, Ismo, Mäkelä, Mika, Laitinen, Annika, Laitinen, Lauri A, Alenius, Harri
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024219/
https://www.ncbi.nlm.nih.gov/pubmed/21205293
http://dx.doi.org/10.1186/1465-9921-12-2
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author Meuronen, Anna
Karisola, Piia
Leino, Marina
Savinko, Terhi
Sirola, Kristiina
Majuri, Marja-Leena
Piirilä, Päivi
Virtanen, Ismo
Mäkelä, Mika
Laitinen, Annika
Laitinen, Lauri A
Alenius, Harri
author_facet Meuronen, Anna
Karisola, Piia
Leino, Marina
Savinko, Terhi
Sirola, Kristiina
Majuri, Marja-Leena
Piirilä, Päivi
Virtanen, Ismo
Mäkelä, Mika
Laitinen, Annika
Laitinen, Lauri A
Alenius, Harri
author_sort Meuronen, Anna
collection PubMed
description BACKGROUND: Asthma leads to structural changes in the airways, including the modification of extracellular matrix proteins such as tenascin-C. The role of tenascin-C is unclear, but it might act as an early initiator of airway wall remodelling, as its expression is increased in the mouse and human airways during allergic inflammation. In this study, we examined whether Th1 or Th2 cells are important regulators of tenascin-C in experimental allergic asthma utilizing mice with impaired Th1 (STAT4-/-) or Th2 (STAT6-/-) immunity. METHODS: Balb/c wildtype (WT), STAT4-/- and STAT6-/- mice were sensitized with intraperitoneally injected ovalbumin (OVA) followed by OVA or PBS airway challenge. Airway hyperreactivity (AHR) was measured and samples were collected. Real time PCR and immunohistochemistry were used to study cytokines and differences in the expression of tenascin-C. Tenascin-C expression was measured in human fibroblasts after treatment with TNF-α and IFN-γ in vitro. RESULTS: OVA-challenged WT mice showed allergic inflammation and AHR in the airways along with increased expression of TNF-α, IFN-γ, IL-4 and tenascin-C in the lungs. OVA-challenged STAT4-/- mice exhibited elevated AHR and pulmonary eosinophilia. The mRNA expression of TNF-α and IFN-γ was low, but the expression of IL-4 was significantly elevated in these mice. OVA-challenged STAT6-/- mice had neither AHR nor pulmonary eosinophilia, but had increased expression of mRNA for TNF-α, IFN-γ and IL-4. The expression of tenascin-C in the lungs of OVA-challenged STAT4-/- mice was weaker than in those of OVA-challenged WT and STAT6-/- mice suggesting that TNF-α and IFN-γ may regulate tenascin-C expression in vivo. The stimulation of human fibroblasts with TNF-α and IFN-γ induced the expression of tenascin-C confirming our in vivo findings. CONCLUSIONS: Expression of tenascin-C is significantly attenuated in the airways of STAT4-/- mice, which may be due to the impaired secretion of TNF-α and IFN-γ in these mice.
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spelling pubmed-30242192011-01-21 Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice Meuronen, Anna Karisola, Piia Leino, Marina Savinko, Terhi Sirola, Kristiina Majuri, Marja-Leena Piirilä, Päivi Virtanen, Ismo Mäkelä, Mika Laitinen, Annika Laitinen, Lauri A Alenius, Harri Respir Res Research BACKGROUND: Asthma leads to structural changes in the airways, including the modification of extracellular matrix proteins such as tenascin-C. The role of tenascin-C is unclear, but it might act as an early initiator of airway wall remodelling, as its expression is increased in the mouse and human airways during allergic inflammation. In this study, we examined whether Th1 or Th2 cells are important regulators of tenascin-C in experimental allergic asthma utilizing mice with impaired Th1 (STAT4-/-) or Th2 (STAT6-/-) immunity. METHODS: Balb/c wildtype (WT), STAT4-/- and STAT6-/- mice were sensitized with intraperitoneally injected ovalbumin (OVA) followed by OVA or PBS airway challenge. Airway hyperreactivity (AHR) was measured and samples were collected. Real time PCR and immunohistochemistry were used to study cytokines and differences in the expression of tenascin-C. Tenascin-C expression was measured in human fibroblasts after treatment with TNF-α and IFN-γ in vitro. RESULTS: OVA-challenged WT mice showed allergic inflammation and AHR in the airways along with increased expression of TNF-α, IFN-γ, IL-4 and tenascin-C in the lungs. OVA-challenged STAT4-/- mice exhibited elevated AHR and pulmonary eosinophilia. The mRNA expression of TNF-α and IFN-γ was low, but the expression of IL-4 was significantly elevated in these mice. OVA-challenged STAT6-/- mice had neither AHR nor pulmonary eosinophilia, but had increased expression of mRNA for TNF-α, IFN-γ and IL-4. The expression of tenascin-C in the lungs of OVA-challenged STAT4-/- mice was weaker than in those of OVA-challenged WT and STAT6-/- mice suggesting that TNF-α and IFN-γ may regulate tenascin-C expression in vivo. The stimulation of human fibroblasts with TNF-α and IFN-γ induced the expression of tenascin-C confirming our in vivo findings. CONCLUSIONS: Expression of tenascin-C is significantly attenuated in the airways of STAT4-/- mice, which may be due to the impaired secretion of TNF-α and IFN-γ in these mice. BioMed Central 2011 2011-01-04 /pmc/articles/PMC3024219/ /pubmed/21205293 http://dx.doi.org/10.1186/1465-9921-12-2 Text en Copyright ©2011 Meuronen et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (<url>http://creativecommons.org/licenses/by/2.0</url>), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Meuronen, Anna
Karisola, Piia
Leino, Marina
Savinko, Terhi
Sirola, Kristiina
Majuri, Marja-Leena
Piirilä, Päivi
Virtanen, Ismo
Mäkelä, Mika
Laitinen, Annika
Laitinen, Lauri A
Alenius, Harri
Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice
title Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice
title_full Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice
title_fullStr Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice
title_full_unstemmed Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice
title_short Attenuated expression of tenascin-c in ovalbumin-challenged STAT4-/- mice
title_sort attenuated expression of tenascin-c in ovalbumin-challenged stat4-/- mice
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3024219/
https://www.ncbi.nlm.nih.gov/pubmed/21205293
http://dx.doi.org/10.1186/1465-9921-12-2
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