1997 Fiscal Year Final Research Report Summary
Regulation of gene expression by macrolides in bronchial epithelial cells
| Project/Area Number |
08670680
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | The Jikei University School of Medicine |
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Principal Investigator |
TANABE Osamu Jikei University School of Medicine, 医学部, 講師 (20236657)
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| Co-Investigator(Kenkyū-buntansha) |
YOSHIMURA Kunihiko Jikei University School of Medicine Assistant Professor, 医学部, 講師 (60246452)
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| Project Period (FY) |
1996 – 1997
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| Keywords | macrolides / diffuse panbronchiolitis / airway epithelium / gene expression / differential display / beta-defensin |
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| Research Abstract |
Diffuse panbronchiolitis is a chronic inflammatory airway disease affecting particularyl respiratory bronchioles. The prognosis of the disease used to be extremely poor because of sustained P seudomonas infection and respiratory failure. However, the introduction of low dose and long term administration of macrolides has dramatically improved its prognosis. Although the mechanism of effectiveness of macrolides therapy is not fully understood, a growing body of evidence suggests it is likely due to the anti-inflammatory and immuno-modulating properties of the agents. To investigate the molecular mechanisms of effectiveness of macrolides, we have utilized differential display analysis (DD) and RT-PCR.HS-24 lung squamous carcinoma cells were incubated in the presence or absence of erythromycin (EM) and/or TNF-alpha for 24hr. After total RNA was extracted, DD was performed and sequenses of defferently expressed mRNA was analyzed. The human beta defensin (hBD-1), expressed in bronchial epit
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helial cells and is thought to have close relationship with biological defense and inflammation, was also analyzed by RT-PCR for its mRNA expression. By DD,several up-regulated genes were detected in cells incubated with EM.Further, multiple up-and down-regulated genes were also obseved when exposed to TNF-alpha after pretreatment with or without EM.Sequencing and homology search analysis of the defferentially expressed cDNAs thus far revealed that one of the clones is 98.9% homologous to human 28S ribosomal RNA.Expression of the hBD-1 gene was downregulated by EM with or without inflammatory stimuli. These data suggest macrolides including EM confer their therapeutic efficacy by up-or down-regulating expression of multiple genes in bronchial epithelial cells and modulating effects on gene expression by cytokines such as TNF-alpha. It is also suggested the modulatory effects of macrolides may be, at least in part, throuth pretein synthesis and hBD-1 is likely to have some roles in biological defense of bronchial epitherial cells. Less
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