These findings cannot exclude the hypothesis of involvement of Akt and MAPK signalling pathways in pathogenesis of IPF. However, further investigation is needed in order to verify these data.

Background and aimToll-like receptors (TLRs), a key component of innate immunity, have recently been implicated in the pathogenesis of interstitial lung diseases (ILDs). As the involvement of TLRs has not yet been fully elucidated, the aim of the current study was to examine the expression of various TLRs in the bronchoalveolar lavage fluid (BALF) of patients with ILDs.Patients and MethodsWe studied prospectively three groups of patients: (1) one group of 35 patients with fibrotic disorders, 16 with idiopathic pulmonary fibrosis (IPF) and 19 with fibrotic interstitial pneumonias associated with collagen tissue disorders (CTD-IPs); (2) one group of 14 patients with pulmonary sarcoidosis; and (3) 11 normal subjects. We evaluated TLR expression with flow cytometry and mRNA expression with real-time PCR.ResultsAn overexpression of TLR-3 mRNA was found in fibrotic disorders (CTD-IPs/IPF) in comparison with sarcoidosis (mean ± SD, 1.104 ± 1.087 versus 0.038 ± 0.03; P = 0.04). Additionally, TLR-3 mRNA was increased in CTD-IPs in comparison with IPF (P = 0.001), sarcoidosis (P = 0.002) and controls (P = 0.05). An upregulation in TLR-7 and -9 mRNA expression was detected in IPF (P = 0.05) and sarcoidosis (P = 0.05), respectively, when compared to controls. A higher percentage of TLR-9-expressing cells was found in BALF of CTD-IPs when compared to IPF (mean ± SD, 36.7 ± 7.06 versus 14.85 ± 3.82; P = 0.025).ConclusionWe observed distinct profiles of TLR expression in fibrotic and granulomatous disorders. It is likely that they could play a key role in the pathogenesis of these diseases and represent future therapeutic targets.

Our results do not support the hypothesis of YY-1 involvement in IPF. However, similar expression of YY-1 gene in two biological samples cannot exclude a possible role of this polymorphic gene in the pathway of IPF. Further studies in a larger scale of patients are needed.

Abstract. Increasing evidence implicates angiogenesis in the pathogenesis of fibrotic lung diseases. Distinct angiogenic profiles may, in part, explain differences in immunopathogenesis, clinical course and prognosis. The aim of the study was to seek evidence of involvement of the angiogenic axis Angiopoietin-1 and -2 and their tyrosine kinase receptor, Tie-2 in pathogenesis of idiopathic pulmonary fibrosis (IPF) and interstitial pneumonias associated to collagen tissue disorders (CTD-IPs). We prospectively studied 36 patients with IPF, 23 patients with CTD-IP and 10 healthy subjects. Ang-1, Ang-2 and Tie-2 mRNA expression and protein levels were measured in bronchoalveolar lavage fluid pellets and supernatants, respectively. A statistically significant decrease of Ang-1 protein level has been found in IPF in comparison to controls (p=0.02). We also detected an increased expression of Ang-2 protein in IPF in comparison to CTD-IPs. A significant co-expression was detected between Ang-2 and Tie-2 in protein level (p=0.007) in IPF group. In conclusion, a suppression of the angiogenetic factor Ang-1 was observed at the protein level in IPF which may be important in the pathogenesis of this devastating disease. A differential angiogenetic profile regarding Ang-2 was detected between IPF and CTD-IPs.

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