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TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis.

Facco M, Cabrelle A, Calabrese F, Teramo A, Cinetto F, Carraro S, Martini V, Calzetti F, Tamassia N, Cassatella MA, Semenzato G, Agostini C - Clin Mol Allergy (2015)

Bottom Line: TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place.Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls.Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy ; Venetian Institute of Molecular Medicine, Padua, Italy.

ABSTRACT

Background: TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place.

Methods: In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects.

Results: Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1.

Conclusions: These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.

No MeSH data available.


Related in: MedlinePlus

Western blotting (a) and confocal microscopy (b) analyses of TL1A and DR3 proteins evaluated in lung T cells and alveolar macrophages obtained from the BAL of two representative cases of patients with active and inactive sarcoidosis and of a control subject. (c) TL1A and DR3 mRNA expression in CD4+ T lymphocytes and alveolar macrophages/monocytes freshly obtained from the lung and the blood of patients affected by active sarcoidosis (black columns), inactive sarcoidosis (grey columns), and from control subjects (white columns). Expression of TL1A and DR3 mRNAs was normalized on GAPDH mRNA. Data are expressed as mean ± SD
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Fig2: Western blotting (a) and confocal microscopy (b) analyses of TL1A and DR3 proteins evaluated in lung T cells and alveolar macrophages obtained from the BAL of two representative cases of patients with active and inactive sarcoidosis and of a control subject. (c) TL1A and DR3 mRNA expression in CD4+ T lymphocytes and alveolar macrophages/monocytes freshly obtained from the lung and the blood of patients affected by active sarcoidosis (black columns), inactive sarcoidosis (grey columns), and from control subjects (white columns). Expression of TL1A and DR3 mRNAs was normalized on GAPDH mRNA. Data are expressed as mean ± SD

Mentions: Western blotting (Fig. 2a) and confocal microscopy analyses (Fig. 2b) of TL1A and DR3 confirmed the higher expression of the two molecules on lung T lymphocytes and alveolar macrophages obtained from patients with active sarcoidosis with respect to patients with the inactive form of the disease and to controls.Fig. 2


TL1A/DR3 axis involvement in the inflammatory cytokine network during pulmonary sarcoidosis.

Facco M, Cabrelle A, Calabrese F, Teramo A, Cinetto F, Carraro S, Martini V, Calzetti F, Tamassia N, Cassatella MA, Semenzato G, Agostini C - Clin Mol Allergy (2015)

Western blotting (a) and confocal microscopy (b) analyses of TL1A and DR3 proteins evaluated in lung T cells and alveolar macrophages obtained from the BAL of two representative cases of patients with active and inactive sarcoidosis and of a control subject. (c) TL1A and DR3 mRNA expression in CD4+ T lymphocytes and alveolar macrophages/monocytes freshly obtained from the lung and the blood of patients affected by active sarcoidosis (black columns), inactive sarcoidosis (grey columns), and from control subjects (white columns). Expression of TL1A and DR3 mRNAs was normalized on GAPDH mRNA. Data are expressed as mean ± SD
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4522997&req=5

Fig2: Western blotting (a) and confocal microscopy (b) analyses of TL1A and DR3 proteins evaluated in lung T cells and alveolar macrophages obtained from the BAL of two representative cases of patients with active and inactive sarcoidosis and of a control subject. (c) TL1A and DR3 mRNA expression in CD4+ T lymphocytes and alveolar macrophages/monocytes freshly obtained from the lung and the blood of patients affected by active sarcoidosis (black columns), inactive sarcoidosis (grey columns), and from control subjects (white columns). Expression of TL1A and DR3 mRNAs was normalized on GAPDH mRNA. Data are expressed as mean ± SD
Mentions: Western blotting (Fig. 2a) and confocal microscopy analyses (Fig. 2b) of TL1A and DR3 confirmed the higher expression of the two molecules on lung T lymphocytes and alveolar macrophages obtained from patients with active sarcoidosis with respect to patients with the inactive form of the disease and to controls.Fig. 2

Bottom Line: TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place.Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls.Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1.

View Article: PubMed Central - PubMed

Affiliation: Department of Medicine, Hematology and Clinical Immunology Branch, Padua University School of Medicine, Padua, Italy ; Venetian Institute of Molecular Medicine, Padua, Italy.

ABSTRACT

Background: TNF-like ligand 1A (TL1A), a recently recognized member of the TNF superfamily, and its death domain receptor 3 (DR3), firstly identified for their relevant role in T lymphocyte homeostasis, are now well-known mediators of several immune-inflammatory diseases, ranging from rheumatoid arthritis to inflammatory bowel diseases to psoriasis, whereas no data are available on their involvement in sarcoidosis, a multisystemic granulomatous disease where a deregulated T helper (Th)1/Th17 response takes place.

Methods: In this study, by flow cytometry, real-time PCR, confocal microscopy and immunohistochemistry analyses, TL1A and DR3 were investigated in the pulmonary cells and the peripheral blood of 43 patients affected by sarcoidosis in different phases of the disease (29 patients with active sarcoidosis, 14 with the inactive form) and in 8 control subjects.

Results: Our results demonstrated a significant higher expression, both at protein and mRNA levels, of TL1A and DR3 in pulmonary T cells and alveolar macrophages of patients with active sarcoidosis as compared to patients with the inactive form of the disease and to controls. In patients with sarcoidosis TL1A was strongly more expressed in the lung than the blood, i.e., at the site of the involved organ. Additionally, zymography assays showed that TL1A is able to increase the production of matrix metalloproteinase 9 by sarcoid alveolar macrophages characterized, in patients with the active form of the disease, by reduced mRNA levels of the tissue inhibitor of metalloproteinase (TIMP)-1.

Conclusions: These data suggest that TL1A/DR3 interactions are part of the extended and complex immune-inflammatory network that characterizes sarcoidosis during its active phase and may contribute to the pathogenesis and to the progression of the disease.

No MeSH data available.


Related in: MedlinePlus