- 學位論文
不同血清型腺病毒感染肺癌細胞株A549所誘發之發炎反應研究
Inflammatory Responses of A549 Lung Adenocarcinoma Induced by Different Serotype Adenovirus Infection
摘要
兒童急性呼吸道感染約5%-10%由腺病毒感染引起，因為腺病毒會造成嚴重的急性呼吸道感染，甚至死亡及結膜感染。人類腺病毒目前已知有51種血清型，6個亞屬(A-F)，造成呼吸道方面感染的腺病毒，主要以血清型第1、2、3、5、6型較常見其中以亞屬B之血清型第3型、第7型為最強的致病源。有關腺病毒造成呼吸道感染之致病機制，至今尚未完全明瞭。一般認為細胞免疫作用，扮演相當重要之角色。而細胞激素在其中所扮演之角色雖然有研究，但不夠完整。同時臨床上亞屬B之血清型第3型、第7型腺病毒臨床症狀常較其他血清型病毒嚴重，此種差異是否與細胞之激素產生有關也是值得探討之課題。 在過去文獻研究過程中，發現2004~2005 年腺病毒分離率大增，腺病毒血清型第3型(Ad3)個案更是大量上升，所以我們以不同血清型腺病毒第1、2、3、5、6型誘發A549細胞之發炎反應,利用ELISA方法檢測IL-6、IL-1、 IL-8及TNF-α的濃度，來探討不同血清型腺病毒致病機制，我們發現腺病毒血清型Ad3所誘發之發炎反應，在8、24、48小時的細胞激素， IL-1、IL-8及TNF-α的濃度都比其他血清型的濃度明顯高，此結果符合過去的文獻說明病情嚴重的病人IL-6、IL-1、 IL-8及TNF-α的濃度都有顯著上升。 本研究利用ELISA方法檢測IL-6、IL-1、IL-8及TNF-α濃度，結果顯示Ad3在本次分析的各血清型腺病毒中，所誘發的IL-1、IL-8及TNF-α濃度呈現最高的現象，但是IL-6的數值分析顯示Ad1比Ad3誘發更高的IL-6。此些差異與不同血清型腺病毒在臨床上引起之症狀之嚴重情形之差異有其相關性存在。因此我們認為使用IL-1、IL-8及TNF-α的濃度，可以幫助醫師在臨床應用上針對病原性較強B屬Ad3評估疾病的嚴重程度，以及監測藥物療效。
關鍵字
腺病毒並列摘要
In children, approximate 5%-10% acute airway infection attributes to adenovirus infection. Adenovirus infection usually cause running nose, fever and further induce severe acute respiratory infection and conjunctival infection, which may lead to death, particularly in children aging less than 6 years old. So far, adenoviruses can be divided into 6 species, which are further subdivided into 51 serotypes. Among the identified adenoviruses, species B (Ad3and Ad7) and species C (Ad1, Ad2, and Ad5) are commonly associated with respiratory tract infections and may persist in children without causing symptoms for years. Intriguingly, Infection of species B adenovirus (Ad3and Ad7) usually causes more severe disease than other serotype species adenovirus. However, the pathogenesis contributing to the severe disease by species B adenovirus remains unclear. Ad3 was the predominant serotype responsible for the outbreak of respiratory adenovirus infections in northern Taiwan during 2004-2005 and was also associated with severe diseases in the outbreak period. It is known that cellular immunity plays an important role in adenovirus infections. Therefore, the present study intends to investigate the patterns of cytokines induced by adenovirus infections, which may distinguish infection by species B adenovirus from the others. By using lung carcinoma cell A549 as the respiratory cell model, production of inflammatory cytokines, including interleukin-1 (IL-1), IL-6, IL-8 and tumor necrosis factor alpha (TNF-α), induced by adenovirus infection was determined by enzyme-linked immunosorbent assay (ELISA). Our findings revealed that Ad3 infection induced the highest level of IL-1, IL-8 and TNF-α production. These results may be helpful to diagnose airway infection by Ad3, which has high probability to cause sever diseases.