Antoniou Katerina M, Soufla Giannoula, Proklou Athanasia, Margaritopoulos George, Choulaki Christiana, Lymbouridou Rena, Samara Katerina D, Spandidos Demetrios A, Siafakas Nikolaos M
Department of Thoracic Medicine, University Hospital, Medical School, University of Crete, Heraklion, 71110 Crete, Greece.
Clin Dev Immunol. 2009;2009:537929. doi: 10.1155/2009/537929. Epub 2010 Feb 14.
We have previously shown a different local and systemic angiogenic profile of CXC chemokines in Idiopathic Pulmonary Fibrosis (IPF) patients compared to sarcoidosis. In particular, sarcoidosis showed an angiostatic microenvironment, as compared with the angiogenic cytokine milieu seen in IPF. Purpose of the Study. Our aim was to further investigate the aforementioned finding by measuring the expression of different chemokines in granulomatous and fibrotic diseases. We estimated the levels of vascular endothelial growth factor (VEGF) and its high-affinity receptor, Flt-1 (fms-like tyrosine kinase 1), in bronchoalveolar lavage fluid (BALF) of patients with IPF and pulmonary sarcoidosis. We have also investigated the mRNA expression of angiogenetic chemokines' receptors such as CXCR2 and CXCR3 and the biological axis of stromal derived factor-1 alpha (SDF-1 alpha or CXCL12 alpha/CXCL12 beta) and receptor, CXCR4.
We studied prospectively three groups of patients: (i) one group of 18 patients with IPF, (ii) one group of 16 patients with sarcoidosis, and (iii) 10 normal subjects.
A statistically significant increase has been detected in VEGF mRNA expression in IPF in comparison with pulmonary sarcoidosis (P = .03). In addition, a significant increase has been measured in CXCL12 alpha in sarcoidosis in comparison to IPF (P = .02). Moreover, a statistically significant decrease has been found in Flt-1 protein levels in pulmonary sarcoidosis in comparison with IPF (P = .03). A significant increase in VEGF (P = .03) and CXCR4 (P = .03) mRNA levels has been also detected in sarcoidosis' patients when compared with healthy controls.
Our data suggest that increased expression of Flt-1 and downregulation of CXCL12 alpha in IPF may further support the hypothesis of a different angiogenetic profile between fibrotic and granulomatous diseases. However, further studies are needed in order to better investigate these enigmatic diseases.
我们之前已经表明，与结节病患者相比，特发性肺纤维化（IPF）患者体内CXC趋化因子的局部和全身血管生成情况有所不同。特别是，结节病表现出血管生成抑制微环境，而IPF则呈现血管生成细胞因子环境。研究目的。我们的目的是通过测量肉芽肿性疾病和纤维化疾病中不同趋化因子的表达，进一步研究上述发现。我们估计了IPF和肺结节病患者支气管肺泡灌洗液（BALF）中血管内皮生长因子（VEGF）及其高亲和力受体Flt-1（fms样酪氨酸激酶1）的水平。我们还研究了血管生成趋化因子受体如CXCR2和CXCR3的mRNA表达，以及基质衍生因子-1α（SDF-1α或CXCL12α/CXCL12β）及其受体CXCR4的生物学轴。
我们前瞻性地研究了三组患者：（i）一组18例IPF患者，（ii）一组16例结节病患者，以及（iii）10名正常受试者。
与肺结节病相比，IPF患者VEGF mRNA表达有统计学意义的增加（P = 0.03）。此外，与IPF相比，结节病患者CXCL12α有显著增加（P = 0.02）。而且，与IPF相比，肺结节病患者Flt-1蛋白水平有统计学意义的降低（P = 0.03）。与健康对照相比，结节病患者的VEGF（P = 0.03）和CXCR4（P = 0.03）mRNA水平也有显著增加。
我们的数据表明，IPF中Flt-1表达增加和CXCL12α下调可能进一步支持纤维化疾病和肉芽肿性疾病之间血管生成情况不同的假说。然而，需要进一步研究以更好地探究这些疑难疾病。
