Moises Selman

..Progress in understanding the fibrogenic mechanisms in the lung is likely to yield more effective therapies...

..An evolving hypothesis proposes that IPF may result from epithelial micro-injuries and abnormal wound healing...

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..These findings indicate that MICA polymorphisms and abnormal expression of the MICA receptor NKG2D might contribute to IPF susceptibility...

..To evaluate the effect of CP-471,474 (Pfizer Global Research and Development; Groton, CT), a broad-spectrum inhibitor of matrix metalloproteinases (MMPs) in an experimental model of emphysema...

..3; CI 1.15-4.97). These findings indicate that polymorphisms of the MMP-1 promoter may confer increased risk for IPF and reveal a putative gene-environment interaction between the -755 MMP-1 polymorphism and smoking in this disease...

..These results confirm a predominant role of the Th1 response in HP and suggest that the control of inflammation by Th2 biased mice may be related with the increase of NKT DN cells and regulatory NK and gammadelta T cells...

..However, PSMB9-RH/PSMB8 KQ haplotype was significantly increased in HP patients (OR = 6.77, CI = 1.34-65.31, p < 0.02). These findings suggest that PSMB8 KQ genotype could increase the risk to develop hypersensitivity pneumonitis...

..These findings indicate that loss of Thy-1 in human lung fibroblasts induces a fibrogenic phenotype...

..These findings indicate that TGF-beta1-induced EMT is reversed by FGF-1 and suggest therapeutic approaches to target this process in IPF...

..However, a subset of patients has a short duration of symptoms with rapid progression to end-stage disease. In this study, we evaluated clinical and molecular features of "rapid" and "slow" progressors with IPF...

..However, the mechanisms involved in their migration, subsequent homing, and local role remain unclear. Matrix metalloproteinases (MMPs) facilitate cell migration and have been implicated in the pathogenesis of pulmonary fibrosis...

..These findings suggest that increased neutrophils and matrix metalloproteinase-9 during the early inflammatory response and adequate thiol reserves are key elements in the fibrotic response after bleomycin-induced pulmonary injury...

..Hypersensitivity pneumonitis (HP) exhibits a diverse outcome. Patients with acute/subacute HP usually improve, whereas patients with chronic disease often progress to fibrosis. However, the mechanisms underlying this difference are unknown...

..In this article, some characteristics of the alveolar epithelium are briefly outlined, and the fibrogenic mechanisms specifically operated by active abnormal epithelial cells are examined...

..07). These findings demonstrate that a variety of histopathologic and imaging patterns are seen in PBD, and the presence of a UIP-like pattern confers the worst prognosis...

..These findings indicate that family history of pulmonary fibrosis is a strong risk factor for IPF. Also, we confirmed that occupational exposures, gastroesophageal reflux and former smoking increase the risk for this disease...

..002, OR=0.07, CI=0.0-0.57). These findings suggest that TAP1 gene polymorphisms are related to HP risk, and highlight the importance of the MHC in the development of this disease...

..FGF-1 alone exhibited similar but lower effects. These findings suggest that FGF-1 can have an antifibrogenic role, inducing apoptosis of fibroblasts and inhibiting myofibroblast differentiation...

..Microchimerism has been implicated in the pathogenesis of autoimmune diseases, especially in those showing increased incidence after childbearing age...

..Our findings suggest that TGF-beta1-induced TIMP3 may be an important mediator in lung fibrogenesis...

..In this review we summarize the current evidence regarding the diagnostic criteria and therapeutic strategies as well as the immunopathological mechanisms putatively implicated in the development of the disease...

..These findings indicate that the SHH pathway is activated in IPF lungs and that SHH may contribute to IPF pathogenesis by increasing the proliferation, migration, extracellular matrix production, and survival of fibroblasts...

..05). These findings demonstrate that many IPF fibroblasts have reduced expression of the proapoptotic p14(ARF) attributable to promoter hypermethylation and indicate that epigenetic mechanisms may underlie their resistance to apoptosis...

..In this article we compare clinical features, smoking history, pulmonary function, estimated systolic pulmonary artery pressure (eSPAP), and mortality in IPF with emphysema vs IPF without emphysematous changes...

..01). These findings suggest that some MHC polymorphisms confer susceptibility to IPF, which might be related with the induction of epithelial cell apoptosis, a critical process in the development of the disease...

..Conclusions: Up-regulation of MMP19 induced by lung injury may play a protective role in the development of fibrosis through the induction of PTGS2...

..This aberrant repair process annihilates the lung architecture leading to the honeycomb remodeling...

..Our findings corroborate the reversibility of bleomycin-induced lung fibrosis and reveal transcriptional signatures that characterize the progression and resolution...

..Corticosteroids are generally used, although their long-term efficacy has not been proved in prospective clinical trials. Lung transplantation should be recommended in cases of progressive end-stage illness...

..These findings suggest that it is possible to identify biomarkers of severe pneumonia and also suggest the therapeutic use of immunomodulatory drugs in patients with severe pneumonia associated with A/H1N1 infection...

..Our results provide additional evidence of a putative relationship between DM2 and idiopathic pulmonary fibrosis. Experimental research is necessary for thorough assessment of the pathogenic mechanisms involved in this association...

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..Consequently, MMPs may play a central role in several interrelated processes observed in fibrosis such as ECM remodeling, basement-membrane breakdown, epithelial-cell apoptosis, cell migration, and angiogenesis...

..Stem cell progenitors of the alveolar epithelial cells and genetic and epigenetic therapies are attractive future approaches for this and other fibrotic lung disorders...

..Likewise, it seems to be implicated in a variety of human diseases including cancer, rheumatoid arthritis, pulmonary emphysema and fibrotic disorders, suggesting that its inhibition or stimulation may open therapeutic avenues...

..Nonetheless, it appears clear that new therapeutic approaches are urgently needed...

..Here, we review the emerging concepts highlighting the putative aging-associated abnormalities involved in some human ILDs...

..In this study, we evaluated the levels of two suppressor proteins (pRb and p53) and two oncogenic proteins (c-Myc and Bcl-2), as well as the apoptotic levels and the presence of human papillomavirus (HPV) in both tumor types...

..These findings indicate that surfactant protein variants may serve as markers to identify subgroups of patients at risk, and we speculate that these contribute to IPF pathogenesis...

..Resistant animals behave as controls. These findings suggest that an imbalance between collagenases and TIMPs, excessive gelatinolytic activity, and epithelial apoptosis participate in the fibrotic response in this experimental model...

..New anti-inflammatory, immunoregulatory, and antifibrotic drugs are urgently needed for this and other interstitial lung diseases...

..005). These data suggest that PaCO2/PaO2 ratio appears to be a predictor of mortality in this subset of patients. Its prospective use has reduced early mortality after surgery less than 1% in the last decade...

..Tetrodotoxin, tetracaine or hexamethonium did not modify the enhanced sensitivity of denuded tracheas to histamine, suggesting that, at least under these experimental conditions, local axon or ganglionic reflexes are not involved...

..These results suggest that fibroblasts from IPF exhibit a profibrotic secretory phenotype, with lower growth rate and increased spontaneous apoptosis...