Genome-Wide Gene Expression Analysis Suggests an Important Role of Suppressed Immunity in Pathogenesis of Kashin-Beck Disease

OBJECTIVE: To investigate the differences between the gene expression profiles in peripheral blood mononuclear cells (PBMC) from normal controls and patients with Kashin-Beck disease (KBD). METHODS: Twenty KBD patients and 12 normal subjects were selected from a KBD-endemic area and divided into four pairs of KBD vs. control (KBD, n = 5 per pair; control, n = 3 per pair). RNAs were respectively isolated from KBD PBMCs and normal PBMCs. Gene expression profiles were analyzed by oligonucleotide microarray. The gene expression profiles in PBMCs from KBD patients and normal controls were compared and the differentially expressed genes were identified. The obtained microarray data was further confirmed by using quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR). RESULTS: Approximately 501 genes, corresponding to 2.4% of the total probe transcripts, showed a 2-fold change in differential expression. 19.4% (97 out of 501)of the differentially expressed genes were commonly detected in all the four pairs. Among the 97 differentially expressed genes, 83 genes were up-regulated and 14 genes were down-regulated, compared with those in the normal controls. Some differentially expressed genes were found to be related to functions such as immunity, metabolism, apoptosis, cystoskeleton and cell movement, and extracellular matrix. The validity of our microarray data were supported by the results of qRT-PCR assay. CONCLUSION: Differences in the PBMC gene expression profile between the KBD patients and the normal controls exhibited a similar pattern among all the four pairs of microarrays examined, indicating that the suppressed immunity may play an important role in the pathogenesis of KBD

Cigarette smoke worsens lung inflammation and impairs resolution of influenza infection in mice

<p>Abstract</p> <p>Background</p> <p>Cigarette smoke has both pro-inflammatory and immunosuppressive effects. Both active and passive cigarette smoke exposure are linked to an increased incidence and severity of respiratory virus infections, but underlying mechanisms are not well defined. We hypothesized, based on prior gene expression profiling studies, that upregulation of pro-inflammatory mediators by short term smoke exposure would be protective against a subsequent influenza infection.</p> <p>Methods</p> <p>BALB/c mice were subjected to whole body smoke exposure with 9 cigarettes/day for 4 days. Mice were then infected with influenza A (H3N1, Mem71 strain), and analyzed 3 and 10 days later (d3, d10). These time points are the peak and resolution (respectively) of influenza infection.</p> <p>Results</p> <p>Inflammatory cell influx into the bronchoalveolar lavage (BALF), inflammatory mediators, proteases, histopathology, viral titres and T lymphocyte profiles were analyzed. Compared to smoke or influenza alone, mice exposed to smoke and then influenza had more macrophages, neutrophils and total lymphocytes in BALF at d3, more macrophages in BALF at d10, lower net gelatinase activity and increased activity of tissue inhibitor of metalloprotease-1 in BALF at d3, altered profiles of key cytokines and CD4+ and CD8+ T lymphocytes, worse lung pathology and more virus-specific, activated CD8+ T lymphocytes in BALF. Mice smoke exposed before influenza infection had close to 10-fold higher lung virus titres at d3 than influenza alone mice, although all mice had cleared virus by d10, regardless of smoke exposure. Smoke exposure caused temporary weight loss and when smoking ceased after viral infection, smoke and influenza mice regained significantly less weight than smoke alone mice.</p> <p>Conclusion</p> <p>Smoke induced inflammation does not protect against influenza infection.</p> <p>In most respects, smoke exposure worsened the host response to influenza. This animal model may be useful in studying how smoke worsens respiratory viral infections.</p

Role of apoptosis in the pathogenesis of COPD and pulmonary emphysema

Chronic obstructive pulmonary disease (COPD) is characterised by chronic inflammation of the airways and progressive destruction of lung parenchyma, a process that in most cases is initiated by cigarette smoking. Several mechanisms are involved in the development of the disease: influx of inflammatory cells into the lung (leading to chronic inflammation of the airways), imbalance between proteolytic and anti-proteolytic activity (resulting in the destruction of healthy lung tissue) and oxidative stress. Recently, an increasing number of data suggest a fourth important mechanism involved in the development of COPD: apoptosis of structural cells in the lung might possibly be an important upstream event in the pathogenesis of COPD. There is an increase in apoptotic alveolar epithelial and endothelial cells in the lungs of COPD patients. Since this is not counterbalanced by an increase in proliferation of these structural cells, the net result is destruction of lung tissue and the development of emphysema. Data from animal models suggest a role for Vascular Endothelial Growth Factor (VEGF) in the induction of apoptosis of structural cells in the lung. Other mediators of apoptosis, such as caspase-3 and ceramide, could be interesting targets to prevent apoptosis and the development of emphysema. In this review, recent data on the role of apoptosis in COPD from both animal models as well as from studies on human subjects will be discussed. The aim is to provide an up to date summary on the increasing knowledge on the role of apoptosis in COPD and pulmonary emphysema

The genetics of chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease caused by the interaction of genetic susceptibility and environmental influences. There is increasing evidence that genes link to disease pathogenesis and heterogeneity by causing variation in protease anti-protease systems, defence against oxidative stress and inflammation. The main methods of genomic research for complex disease traits are described, together with the genes implicated in COPD thus far, their roles in disease causation and the future for this area of investigation

Conclusion

Summary. — Caucasus and Alps differ from one another in their structure, strongly ordered by overthrusts; In the Alps are more longitudinal valleys than in the Caucasus, where it is a lot of transverse streams, Glaciers played a different part: classic glaciation in the Alps does not exist in the Caucasus mountains where, to day glaciers are larger, more variegated. Caucasian flora, more wealthy, is too made of more patterns. Concerning appointement, late changes in the Alps were deeper and more savage, especially at high altitude, with combined ressorts development.Résumé. — Caucase et Alpes diffèrent par leur structure, plus fortement réglée par les charriages dans les Alpes. Les Alpes ont davantage de vallées longitudinales que le Caucase où prédominent les tracés transversaux. Le rôle des glaciers a été différent et l'on ne retrouve pas les glaciations classiques des Alpes, dans un Caucase où les glaciers actuels sont plus étendus, mais plus variés. La flore du Caucase, plus riche, offre aussi des types plus nombreux. Sur le plan de l'aménagement, les transformations récentes des Alpes ont été plus profondes et plus brutales, surtout à haute altitude avec le développement des stations intégrées.Guerassimov I.P., Zimina R.P., Kotliakov V.M., Lilienberg D.A., Préobrajenski V.S. Conclusion. In: Revue de géographie alpine, tome 69, n°2, 1981. pp. 357-368

Conclusion

Summary. — Caucasus and Alps differ from one another in their structure, strongly ordered by overthrusts; In the Alps are more longitudinal valleys than in the Caucasus, where it is a lot of transverse streams, Glaciers played a different part: classic glaciation in the Alps does not exist in the Caucasus mountains where, to day glaciers are larger, more variegated. Caucasian flora, more wealthy, is too made of more patterns. Concerning appointement, late changes in the Alps were deeper and more savage, especially at high altitude, with combined ressorts development.Résumé. — Caucase et Alpes diffèrent par leur structure, plus fortement réglée par les charriages dans les Alpes. Les Alpes ont davantage de vallées longitudinales que le Caucase où prédominent les tracés transversaux. Le rôle des glaciers a été différent et l'on ne retrouve pas les glaciations classiques des Alpes, dans un Caucase où les glaciers actuels sont plus étendus, mais plus variés. La flore du Caucase, plus riche, offre aussi des types plus nombreux. Sur le plan de l'aménagement, les transformations récentes des Alpes ont été plus profondes et plus brutales, surtout à haute altitude avec le développement des stations intégrées.Guerassimov I.P., Zimina R.P., Kotliakov V.M., Lilienberg D.A., Préobrajenski V.S. Conclusion. In: Revue de géographie alpine, tome 69, n°2, 1981. pp. 357-368