Investigation of Toll-like receptors in the pathogenesis of fibrotic and granulomatous disorders: a bronchoalveolar lavage study

Margaritopoulos, G; Αντωνίου, Κατερίνα; Karagiannis, Konstantinos; Samara, Katerina D.; Lasithiotaki, Ismini; Vassalou, Evi; Lymbouridou, Rena; Koutala, Helen; Siafakas, Nikos M.

doi:10.1186/1755-1536-3-20

Cited by 29 publications

(20 citation statements)

References 41 publications

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“…Meneghin et al (16) have reported an increased TLR9 expression in biopsies from patients with idiopathic interstitial pneumonias (usual interstitial pneumonia, non-specific interstitial pneumonia) when compared with normal lung biopsies and this expression was localized to areas of marked interstitial fibrosis. In a previous study by our group, addressing TLR involvement in fibrotic and granulomatous disorders, an overexpression of TLR-7 mRNA was shown in patients with IPF versus healthy controls, in agreement with these current results and underlining the possible role of TLRs in the pathogenesis of fibrotic disease (40).…”

Section: Discussionsupporting

confidence: 92%

Expression profiles of Toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis

et al. 2012

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Abstract.Patients with idiopathic pulmonary fibrosis (IPF) have a higher incidence of lung cancer. The role of Toll-like receptors (TLRs), a key component of the innate immunity, in interstitial lung diseases (ILDs) and lung cancer pathogenesis is not clarified. TLR2, TLR3, TLR4, TLR7, TLR8 and TLR9 mRNA expression was quantitatively measured by real-time reverse transcriptase polymerase chain reaction (RT-PCR) in bronchoalveolar lavage fluid (BALF) of 16 IPF patients, 16 non-small cell lung cancer (NSCLC) patients and 9 control subjects. TLR2, TLR3, TLR4 and TLR9 protein expression was assessed on BALF T-lymphocytes using flow cytometry. TLR3 mRNA expression was significantly higher in NSCLC compared to IPF (p= 0.023) and controls (p= 0.001). TLR7 mRNA expression levels were significantly higher in both NSCLC and IPF groups compared to controls (p= 0.029, p= 0.009). TLR9 expression at the mRNA level was significantly higher in both NSCLC and IPF groups compared to controls (p=0.01, p=0.001). Finally, TLR2 mRNA expression was significantly higher in IPF patients compared to controls (p= 0.042). Flow cytometry revealed decreased TLR3 and TLR9 expression in IPF patients compared to the NSCLC group (p= 0.02, p= 0.014) and decreased TLR9 expression in IPF compared with the controls (p= 0.04). TLR2 protein expression was significantly higher in IPF patients compared to NSCLC (p=0.04). Increased expression of endosomal TLRs in NSCLC patients and elevated expression of TLR2 in pulmonary fibrosis are the main results of this study. These results do not provide support for a common TLR pathway hypothesis between NSCLC and IPF.

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Section: Discussionsupporting

confidence: 92%

Expression profiles of Toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis

et al. 2012

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“…Differential TLRs expression profiles including TLR2 have been identified between patients with IPF and lung cancer; however, results are more descriptive rather than definitive and are limited by the small number of patients enrolled in the study (Samara et al, 2012). Results did not reproduce findings of an earlier study by the same group of investigators where neither TLR2 nor TLR4 were among the upregulated TLRs between patients with IPF and control subjects (Margaritopoulos et al, 2010). Further studies are sorely needed to address the efficacy of extracellular TLRs as biomarkers of IPF development and progression.…”

Section: Toll-like Receptors In Pulmonary Fibrosiscontrasting

confidence: 72%

“…TLR9 mRNA expression was upregulated both in the BALF and lung tissue of patients with IPF compared to controls and patients with lung cancer and connective tissue disorders-associated interstitial pneumonia (Margaritopoulos et al, 2010;Meneghin et al, 2008;Samara et al, 2012). Interestingly, topographic analysis within IPF lungs revealed distinct TLR9 expression profiles between upper and lower lobes that were positively associated with the extent and severity of fibrotic lesions (Trujillo et al, 2010).…”

Section: Tlr9mentioning

confidence: 90%

Toll-like receptors in the pathogenesis of pulmonary fibrosis

Karampitsakos

Woolard

Bouros

et al. 2017

European Journal of Pharmacology

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“…cDNA was synthesized using the Strascript reverse transcriptase kit (Stratagene, La Jolla, CA, USA) as previously described (14).…”

Section: Rna Isolation and Rt-pcrmentioning

confidence: 99%

Investigation of angiogenetic pathways in nasal polyposis

et al. 2012

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Abstract. Tissue angiogenesis is a complex phenomenon that results in the growth of new blood vessels from the microcirculation. This process has been known to play a crucial role in tumor growth as well as several benign diseases. The aim of this study was to assess mRNA expression of various angiogenic factors and chemokines in nasal polyps and compare the results to normal nasal mucosa. mRNA expression was measured using real-time RT-PCR for the following angiogenic factors and chemokines: VEGF, VEGFR-1, Ang-1, Ang-2, Tie-2A, Tie-2B, SDF-1α, SDF-1β, CXCR4 and YY1. Biopsy specimens from nasal polyps in the polyposis group and middle turbinates in the control group were studied. A total of 18 nasal polyposis patients were studied and compared to 10 control subjects. Results showed VEGF, VEGFR-1, Ang-1, Ang-2, Tie-2A, Tie-2B, SDF-1α and SDF-1β mRNA expression to be significantly higher in nasal polyposis patients compared to the control group (p<0.05). The findings of this study support the role of angiogenic growth factors in the pathogenenesis of nasal polyposis. Further studies are required to confirm these results and evaluate potential clinical implications. IntroductionNasal polyposis (NP) constitutes a chronic inflammatory disease of the nose and sinuses characterized by the appearance of protruding tissue swellings of the nasal mucosa. These swellings most commonly originate from the middle meatus and anterior ethmoids. On histologic examination, they are typically characterized by proliferation of the epithelial layer, glandular hyperplasia, thickening of the basal membrane, focal fibrosis, edema and cellular infiltration of the stromal layer. Nasal polyps are relatively common in the general population and significantly affect patient quality of life. Despite these facts, etiology of the disease remains largely unknown (1-4).Tissue angiogenesis is a complex phenomenon that results in the growth of new blood vessels from the microcirculation (5-7). This process has been known to play a crucial role in tumor growth, where it is regarded as a prerequisite allowing for the expansion of tumor populations beyond the size restricted by oxygen and nutrient diffusion (6). It also facilitates tumor progression and metastasis by causing degradation of the epithelial basement membrane and providing cancer cells with new capillaries for entering the circulation (7,8).Increasing evidence shows that angiogenesis may also play a critical role in benign disorders (9,10). The phenomenon, appearing in the form of growth of new blood vessels or the enlargement of existing ones, has been strongly associated with airway remode ling in chronic asthma and chronic obstructive pulmonary disease (11,12). In addition, using immunohistochemistry it has been shown that vascular endothelial growth factor (VEGF), possibly the most important driver of angiogenesis, along with its receptors, are strongly expressed in nasal polyp tissues, thus supporting a role in the development of chronic inflammation and edema in this disease (13).Re...

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Investigation of Toll-like receptors in the pathogenesis of fibrotic and granulomatous disorders: a bronchoalveolar lavage study

Cited by 29 publications

References 41 publications

Expression profiles of Toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis

Expression profiles of Toll-like receptors in non-small cell lung cancer and idiopathic pulmonary fibrosis

Toll-like receptors in the pathogenesis of pulmonary fibrosis

Investigation of angiogenetic pathways in nasal polyposis

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