Expression of CTGF and TNFa in alveolar macrophages of patients with idiopathic pulmonary fibrosis before and after treatment with azathioprine or interferon-γ-1b

SUMMARY.Backgrou nd: Idiopathic pulmonary fibrosis (IPF) is a fatal lungdisorder the aetiology of which is unknown and for which there isno effective therapy. Connective tissue growth factor (CTGF) andtumour necrosis factor alpha (TNFα) have been reported to participatesignificantly in the pathogenesis of the disease. The role of alveolarmacrophages in the expression of these cytokines remains unclear.Materials and Methods: Samples of bronchoalveolar lavagefluid (BALF) derived from 20 newly diagnosed patients with IPF beforeand after 6 months of treatment with either interferon (IFN-γ-1b) andprednisolone (10 patients) or azathioprine (AZA) and prednisolone(10 patients) and from 10 normal subjects (control group) were usedfor the analysis of CTGF and TNFα protein expression in the alveolarmacrophages. The effectiveness of the two drug regimes on thepulmonary function tests (FEV1, FVC, DLCO) and PaO2 and PaCO2 ofthe patients with IPF was investigated. Results: Decreased CTGFprotein expression was detected in the patients with IPF comparedwith the control group (p=0.001). TNFα expression in IPF patientsdid not differ from that of the normal control subjects. Neither ofthe drug regimes affected the protein expression of these factorsorthe pulmonary function parameters. Co nclusion: These findingssuggest that the alveolar macrophages are not the main source ofCTGF and TNFα in IPF. Treatment with either AZA or IFN-γ-1b did notresult in any significant change in the protein expression of thesefactors. Pneumon 2011, 24(2):149-156

Expression of Hypoxia-Inducible Factor (HIF)-1a-Vascular Endothelial Growth Factor (VEGF)-Inhibitory Growth Factor (ING)-4- axis in sarcoidosis patients

Abstract Background Sarcoidosis is a granulomatous disorder of unknown etiology. The term of immunoangiostasis has been addressed by various studies as potentially involved in the disease pathogenesis. The aim of the study was to investigate the expression of the master regulator of angiogenesis hypoxia inducible factor (HIF)-1a – vascular endothelial growth factor (VEGF)- inhibitor of growth factor 4-(ING4) - axis within sarcoid granuloma. Methods A total of 37 patients with sarcoidosis stages II-III were recruited in our study. Tissue microarray technology coupled with immunohistochemistry analysis were applied to video-assisted thoracoscopic surgery (VATS) lung biopsy samples collected from 37 sarcoidosis patients and 24 controls underwent surgery for benign lesions of the lung. Computerized image analysis was used to quantify immunohistochemistry results. qRT-PCR was used to assess HIF-1a and ING4 expression in 10 sarcoidosis mediastinal lymph node and 10 control lung samples. Results HIF-1a and VEGF-ING4 expression, both in protein and mRNA level, was found to be downregulated and upregulated, respectively, in sarcoidosis samples compared to controls. Immunohistochemistry coupled with computerized image analysis revealed minimal expression of HIF-1a within sarcoid granulomas whereas an abundant staining of ING4 and VEGF in epithelioid cells was also visualized. Conclusions Our data suggest an impairment of the HIF-1a – VEGF axis, potentialy arising by ING4 overexpression and ultimately resulting in angiostasis and monocyte recruitment within granulomas. The concept of immunoangiostasis as a possible protection mechanism against antigens of infectious origin needs further research to be verified.</p