TY - JOUR
T1 - Increased pulmonary neurotrophin protein expression in idiopathic interstitial pneumonias
AU - Ricci, Alberto
AU - Graziano, Paolo
AU - Bronzetti, Elena
AU - Saltini, Cesare
AU - Sciacchitano, Salvatore
AU - Cherubini, Emanuela
AU - Renzoni, Elisabetta
AU - Du Bois, Roland M.
AU - Grutters, Jan C.
AU - Mariotta, Salvatore
PY - 2007/3
Y1 - 2007/3
N2 - Background and aim of the study: Idiopathic interstitial pneumoniae (IIPs) are characterized by fibroblast proliferation, extracellular matrix deposition and progressive lung function impairment. Because effective therapeutic strategies still remain limited, research has been directed toward the identification of novel targets for additional therapeutic options. The neurotrophins (NTs) nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and NT-3, beside their importance in nervous, endocrine and immune system activities, participate in chronic inflammatory disorders and in repair processes. Methods: We have investigated NT and high and low affinity NT receptor expression in IIPs using immunoblots and immunohistochemistry. Fourteen idiopatic pulmonary fibrosis/usual interstitial pneumoniae (IPF/UIP), eight non specific pneumoniae (NSIP) and eight respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) were analyzed. Results: Immunoblots revealed that NT and high affinity NT receptor proteins were more abundantly expressed in IPF/UIP than NSIP and RB-ILD patients. In RB-ILD, a faint expression of NT-3 and NT receptors were detected. NT and NT receptor immunostaining was detected in interstitial cells from IPF/UIP, NSIP and RB-ILD patients by immunohistochemistry. Fibroblastic foci in IPF/UIP strongly stained for BDNF and its high affinity receptor TrkB and in lesser amount for NGF, NT-3 and their respective high affinity receptors TrkA and TrkC. Furthermore, in fibroblast culture derived from IPF/UIP patients, the proliferation rate of primary culture and clones derived from primary lines was stimulated by BDNF but down regulated by NT-3. In contrast, NGF did not influence IPF/UIP fibroblasts proliferation. Conclusions: Our data suggest that that NTs may exert differential activities on lung fibroblasts and may be considered as potential regulatory molecules influencing fibroblast behavior in IPF/UIP patients. Therefore, NTs may play a role in IIPs patho-physiology representing novel potential therapeutic targets.
AB - Background and aim of the study: Idiopathic interstitial pneumoniae (IIPs) are characterized by fibroblast proliferation, extracellular matrix deposition and progressive lung function impairment. Because effective therapeutic strategies still remain limited, research has been directed toward the identification of novel targets for additional therapeutic options. The neurotrophins (NTs) nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and NT-3, beside their importance in nervous, endocrine and immune system activities, participate in chronic inflammatory disorders and in repair processes. Methods: We have investigated NT and high and low affinity NT receptor expression in IIPs using immunoblots and immunohistochemistry. Fourteen idiopatic pulmonary fibrosis/usual interstitial pneumoniae (IPF/UIP), eight non specific pneumoniae (NSIP) and eight respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) were analyzed. Results: Immunoblots revealed that NT and high affinity NT receptor proteins were more abundantly expressed in IPF/UIP than NSIP and RB-ILD patients. In RB-ILD, a faint expression of NT-3 and NT receptors were detected. NT and NT receptor immunostaining was detected in interstitial cells from IPF/UIP, NSIP and RB-ILD patients by immunohistochemistry. Fibroblastic foci in IPF/UIP strongly stained for BDNF and its high affinity receptor TrkB and in lesser amount for NGF, NT-3 and their respective high affinity receptors TrkA and TrkC. Furthermore, in fibroblast culture derived from IPF/UIP patients, the proliferation rate of primary culture and clones derived from primary lines was stimulated by BDNF but down regulated by NT-3. In contrast, NGF did not influence IPF/UIP fibroblasts proliferation. Conclusions: Our data suggest that that NTs may exert differential activities on lung fibroblasts and may be considered as potential regulatory molecules influencing fibroblast behavior in IPF/UIP patients. Therefore, NTs may play a role in IIPs patho-physiology representing novel potential therapeutic targets.
KW - Fibroblasts
KW - Interstitial lung diseases
KW - Neurotrophins
UR - http://www.scopus.com/inward/record.url?scp=36549038139&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=36549038139&partnerID=8YFLogxK
M3 - Article
C2 - 18069415
AN - SCOPUS:36549038139
VL - 24
SP - 13
EP - 23
JO - Sarcoidosis Vasculitis and Diffuse Lung Diseases
JF - Sarcoidosis Vasculitis and Diffuse Lung Diseases
SN - 1124-0490
IS - 1
ER -