Enhanced CCL7 and CCR5 Gene Expression in Usual Interstitial Pneumonia

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Authors
Choi, Esther S.
Issue Date
2004
Type
Thesis
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en_US
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Abstract
There has been a struggle to diagnose and manage idiopathic interstitial pneumonia, where the etiology of the disease is unknown and challenging to investigate. There has been considerable research effort directed toward elucidating the cellular and molecular mechanisms through which fibroblasts are triggered and remain activated during progressive, fibrosing disease of the lung parenchyma. Idiopathic pulmonary fibrosis (IPF) or otherwise known as Usual Interstitial Pneumonia (UIP) is a relentless progressive disease, which usually leads to death within 5 years of diagnosis. Symptoms of UIP diagnosed patients include dyspnea, restrictive lung dysfunction and impaired gas exchange. It is seen through this study that chemokines are increased and may contribute to the remodeling events in Idiopathic Interstitial Pneuomonia (lIP). Differentiating between the different subtypes of lIP is the focus of this study. Therapies for some of the lIP types have been inefficient and unsatisfactory. Concomitant expression of inflammatory CC chemokines and their corresponding receptors in surgical lung biopsies (SLBs) obtained at disease diagnosis was done in order to identify each form of lIP according to their factors that activate pulmonary fibrosis. Gene Array analysis helped examine the upper and lower lobe of SLBs from UIP patients. There was an increase in CCR5 gene expression in the SLBs of the UIP patient group relative to those with nonspecific interstitial pneumonia (NSIP). Respiratory bronchiolhatory bronchiol ELISA protein analysis of the SLBs obtained from patients suspected of having a form of lIP showed increased expression of CCL7 and CCL22 gene in UIP patients and increased expression of CCL5 (RANTES) in NSIP-fibrotic patients. This study has provided further support that inflammatory CC chemokine ligands and CC chemokine ligand receptors are highly expressed in SLBs obtained from lIP patients compared to SLBs from non-lIP patients.
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37 p.
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