PMID- 18069415 OWN - NLM STAT- MEDLINE DCOM- 20080211 LR - 20161021 IS - 1124-0490 (Print) IS - 1124-0490 (Linking) VI - 24 IP - 1 DP - 2007 Mar TI - Increased pulmonary neurotrophin protein expression in idiopathic interstitial pneumonias. PG - 13-23 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. FAU - Ricci, Alberto AU - Ricci A AD - Dipartimento di Scienze Cardiovascolari e Respiratorie, Universita di Roma La Sapienza, Ospedale Sant'Andrea, Via di Grottarossa, 1035-1039 00189 Roma. alberto.ricci@uniroma1.it FAU - Graziano, Paolo AU - Graziano P FAU - Bronzetti, Elena AU - Bronzetti E FAU - Saltini, Cesare AU - Saltini C FAU - Sciacchitano, Salvatore AU - Sciacchitano S FAU - Cherubini, Emanuela AU - Cherubini E FAU - Renzoni, Elisabetta AU - Renzoni E FAU - Du Bois, Roland M AU - Du Bois RM FAU - Grutters, Jan C AU - Grutters JC FAU - Mariotta, Salvatore AU - Mariotta S LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - Italy TA - Sarcoidosis Vasc Diffuse Lung Dis JT - Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG JID - 9610928 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) RN - 9061-61-4 (Nerve Growth Factor) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Adult MH - Aged MH - Brain-Derived Neurotrophic Factor/analysis/metabolism MH - Female MH - Fibroblasts/cytology/metabolism MH - Humans MH - Immunohistochemistry MH - Lung/*metabolism MH - Lung Diseases, Interstitial/*metabolism MH - Male MH - Middle Aged MH - Nerve Growth Factor/analysis/metabolism MH - Nerve Growth Factors/analysis/*metabolism MH - Neurotrophin 3/analysis/metabolism MH - Pulmonary Fibrosis/*metabolism MH - Receptor Protein-Tyrosine Kinases/*metabolism EDAT- 2007/12/12 09:00 MHDA- 2008/02/12 09:00 CRDT- 2007/12/12 09:00 PHST- 2007/12/12 09:00 [pubmed] PHST- 2008/02/12 09:00 [medline] PHST- 2007/12/12 09:00 [entrez] PST - ppublish SO - Sarcoidosis Vasc Diffuse Lung Dis. 2007 Mar;24(1):13-23.