The TGF-beta-Pseudoreceptor BAMBI is strongly expressed in COPD lungs and regulated by nontypeable Haemophilus influenzae

被引:45
作者
Droemann, Daniel [1 ]
Rupp, Jan [1 ,2 ]
Rohmann, Kristina [1 ]
Osbahr, Sinia [1 ]
Ulmer, Artur J. [3 ]
Marwitz, Sebastian
Roeschmann, Kristina [3 ]
Abdullah, Mahdi
Schultz, Holger
Vollmer, Ekkehard
Zabel, Peter [1 ,4 ]
Dalhoff, Klaus [1 ]
Goldmann, Torsten
机构
[1] Univ Schleswig Holstein, Med Clin 3, D-23538 Lubeck, Germany
[2] Univ Schleswig Holstein, Inst Med Microbiol & Hyg, D-23538 Lubeck, Germany
[3] Res Ctr Borstel, Dept Immunol & Cell Biol, D-23845 Borstel, Germany
[4] Res Ctr Borstel, Med Clin, D-23845 Borstel, Germany
关键词
CELLS TYPE-II; AIRWAY INFLAMMATION; IMMUNE-RESPONSES; PULMONARY; EXACERBATIONS; FIBROSIS; MACROPHAGES; PNEUMONIAE; INFECTION; APOPTOSIS;
D O I
10.1186/1465-9921-11-67
中图分类号
R56 [呼吸系及胸部疾病];
学科分类号
摘要
Background: Nontypeable Haemophilus influenzae (NTHI) may play a role as an infectious trigger in the pathogenesis of chronic obstructive pulmonary disease (COPD). Few data are available regarding the influence of acute and persistent infection on tissue remodelling and repair factors such as transforming growth factor (TGF)-beta. Methods: NTHI infection in lung tissues obtained from COPD patients and controls was studied in vivo and using an in vitro model. Infection experiments were performed with two different clinical isolates. Detection of NTHI was done using in situ hybridization (ISH) in unstimulated and in in vitro infected lung tissue. For characterization of TGF-beta signaling molecules a transcriptome array was performed. Expression of the TGF-pseudoreceptor BMP and Activin Membrane-bound Inhibitor (BAMBI) was analyzed using immunohistochemistry (IHC), ISH and PCR. CXC chemokine ligand (CXCL)-8, tumor necrosis factor (TNF)-alpha and TGF-beta expression were evaluated in lung tissue and cell culture using ELISA. Results: In 38% of COPD patients infection with NTHI was detected in vivo in contrast to 0% of controls (p < 0.05). Transcriptome arrays showed no significant changes of TGF-beta receptors 1 and 2 and Smad-3 expression, whereas a strong expression of BAMBI with upregulation after in vitro infection of COPD lung tissue was demonstrated. BAMBI was expressed ubiquitously on alveolar macrophages (AM) and to a lesser degree on alveolar epithelial cells (AEC). Measurement of cytokine concentrations in lung tissue supernatants revealed a decreased expression of TGF-beta (p < 0.05) in combination with a strong proinflammatory response (p < 0.01). Conclusions: We show for the first time the expression of the TGF pseudoreceptor BAMBI in the human lung, which is upregulated in response to NTHI infection in COPD lung tissue in vivo and in vitro. The combination of NTHI-mediated induction of proinflammatory cytokines and inhibition of TGF-beta expression may influence inflammation induced tissue remodeling.
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