Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia (UIP) is the severest form of idiopathic interstitial pneumonia for which therapeutic targets are needed. Surgical lung biopsy specimens from IPF/UIP patients exhibit focal expression of CC chemokine receptor (CCR) 7, but the identity of these CCR7-positive cells is unknown. The purpose of the present study was to examine the functional and signalling significance of CCR7 expression of primary fibroblasts grown from IPF/UIP and normal surgical lung biopsy specimens. Primary fibroblasts were cultured from surgical lung biopsy specimens from IPF/UIP and normal patients. Fibroblasts treated with or without CC chemokine ligand (CCL) 21 were analysed for functional, transcriptional and proteomic differences using immunocytochemical analysis, gene arrays, Taqman real-time PCR, and migration, proliferation and Western blot assays. CCR7 was expressed by IPF/UIP fibroblasts, but not normal fibroblasts. IPF/UIP fibroblasts, but not normal fibroblasts, showed significant migratory and proliferative responses when exposed to CCL21, which were inhibited by pertussis toxin or neutralising antibodies to CCR7. Exposure of IPF/UIP fibroblasts to CCL21 altered the phosphorylation status of mitogen-activated protein kinase kinase 1/2, extracellular signal-regulated kinase 1/2 and ribosomal S6 kinase (90 kDa) in these cells; this was abrogated by pertussis toxin or CCR7-specific small interfering RNA. Together, these data demonstrate that CC chemokine ligand 21 modulates the functional properties of idiopathic pulmonary fibrosis/usual interstitial pneumonia fibroblasts, but not normal fibroblasts.
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PMID:Idiopathic pulmonary fibrosis fibroblasts migrate and proliferate to CC chemokine ligand 21. 1733 65

The lymphatic system has several physiological roles, including fluid homeostasis and the activation of adaptive immunity by fluid drainage and cell transport. Lymphangiogenesis occurs in adult tissues during various pathologic conditions. In addition, lymphangiogenesis is closely linked to capillary angiogenesis, and the balanced interrelationship between capillary angiogenesis and lymphangiogenesis is essential for maintaining homeostasis in tissues. Recently, an increasing body of information regarding the biology of lymphatic endothelial cells has allowed us to immunohistochemically characterize lymphangiogenesis in several lung diseases. Particular interest has been given to the interstitial lung diseases. Idiopathic interstitial pneumonias (IIPs) are characterized by heterogeneity in pathologic changes and lesions, as typified by idiopathic pulmonary fibrosis/usual interstitial pneumonia. In IIPs, lymphangiogenesis is likely to have different types of localized functions within each disorder, corresponding to the heterogeneity of lesions in terms of inflammation and fibrosis. These functions include inhibitory absorption of interstitial fluid and small molecules and maturation of fibrosis by excessive interstitial fluid drainage, caused by an unbalanced relationship between capillary angiogenesis and lymphangiogenesis and trafficking of antigen-presenting cells and induction of fibrogenesis via CCL21 and CCR7 signals. Better understanding for regional functions of lymphangiogenesis might provide new treatment strategies tailored to lesion heterogeneity in these complicated diseases.
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PMID:Lymphangiogenesis and Lesion Heterogeneity in Interstitial Lung Diseases. 2682 55