Ho, SP

Lam, WK

Leung, YH

Mak, JCW

Newton, R

Sun, JZ

Tipoe, GL

Tsang, KWT

Hong Kong Medical Journal

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TitleDifferential regulation of cytokine-and phorbol ester-inducedactivation of nuclear factor kappa B by Pseudomonasaeruginosa pyocyanin in human airway epithelial cellsAuthor(s) Mak, JCW; Newton, R; Tipoe, GL; Leung, YH; Ho, SP; Sun, JZ;Lam, WK; Tsang, KWTCitationThe 8th Medical Research Conference Abstracts, Hong KongMedical Journal, Hong Kong, China, 25-26 January 2003, v. 9 n. 1Supp 1, p. 92, abstract no. RM-16Issued Date 2003URL http://hdl.handle.net/10722/45660Rights Creative Commons: Attribution 3.0 Hong Kong License92      HKMJ Vol 9 No 1 February 2003 SupplementMolecular and conventional epidemiology of tuberculosis in Hong Kong—apopulation-based prospective studyChan-Yeung M, Tam CM, Leung CC, Wang J, Yew WW, Lam CW, Kam KM. The University of Hong Kong, the Hong KongGovernment Tuberculosis and Chest Service, Tuberculosis Reference Laboratory, Department of Health, Grantham andRuttonjee Hospital, Hong Kong, SAR.Objective: The purpose of the study was to determine the pattern of transmission of tuberculosis in Hong Kong byconducting a prospective molecular and conventional epidemiology studyMethods: All notified patients residing in the Island of Hong Kong with culture positive tuberculosis were recruitedfor the study from May 1999 to October 2000. Contact investigation was carried out and demographic and clinicalinformation was obtained. The restriction fragment length polymorphism (RFLP) technique was used to determineDNA patterns of M. tuberculosis isolates.Results: Of the 702 isolates that had RFLP analysis with the IS6110 probe, only 11 (1.6%) had 5 bands or less. 169(24.5%) of the 691 remaining patients had sputum isolates that belonged to clusters. Significant predictors ofbelonging to clusters were permanent residency vs new or nonresidents (RR 4.57 95% 1.39-14.9) in Hong Kongand a history of travel to Mainland China in the past 2 years (RR 1.74, 95% CI 1.22-2.47). Risk factors such asalcohol and drug abuse, imprisonment, and HIV infection were not important.Conclusion: While the majority of active tuberculosis in Hong Kong is due to reactivation, there is still a proportionof disease due to recent transmission that is higher than expected. The lack of epidemiological link in the majorityof clustered patients suggests transmission of disease could be through casual contact.Supported by a grant from the HK RGC No: HKU7272/00MDifferential regulation of cytokine-and phorbol ester-induced activation of nuclearfactor kappa B by Pseudomonas aeruginosa pyocyanin in human airway epithelial cellsJCW Mak, *R Newton, #GL Tipoe, R Leung, SP Ho, J Sun, WK Lam, KWT Tsang. *Department of Thoracic Medicine,Imperial College @ NHLI, London, UK and Departments of Medicine and #Anatomy, University of Hong Kong, QueenMary Hospital, Hong Kong SAR.Introduction: Non-cystic fibrosis bronchiectasis is a common disease in Chinese, and its pathogenesis is poorlyunderstood. Gradual destruction of the airways occurs from a combination of chronic airway inflammation andinfection. Many patients eventually harbour Pseudomonas aeruginosa (PA), which produces pyocyanin (PYO), ablue phenazine pigment, in their lower respiratory tract. This study investigates the effects of PYO on cytokine- andphorbol ester-induced activation of NFkappaB in stable transfected A549 cells.Method: The human lung epithelial cell line, A549, was stably transfected with the reporter gene construct(p6kappaBtklucneo) containing six tandem NFkappaB motifs (GGGACTTTCC), and subsequently maintained inmedium containing 0.5mg/ml G-418. After treatment for 6h with cytokines and drugs, cells were harvested inreporter lysis buffer by one freeze-thaw cycle. Bioluminescence in the cell lysates was assayed using a commer-cially available luciferase reporter gene assay kit (Promega).Results: Cytokines (IL-1beta or TNF-alpha) or phorbol 12,13-dibutyrate (PDBu) activated NFkappaB-drivenluciferase activity in a dose-dependent manner. In the presence of pyocyanin, the IL-1beta- and TNF-alpha-inducedactivation was significantly attenuated [1.0 ± 0.1 vs 0.43 ± 0.04 and 0.45 ± 0.05 for cytokine alone and PYO plusIL-1beta (1ng/ml) or plus TNF-alpha (10ng/ml) respectively; n = 4 - 5], while the PDBu-induced activationwas significantly potentiated (1.0 ± 0.03 vs 1.46 ± 0.16 for PDBu alone and PYO plus PDBu at 10-7Mrespectively; n = 4).Conclusion: We conclude that potentiation of NFkappaB-dependent transcription by PDBu in PYO-treated cellsmay imply the involvement of PKC pathway in the chronic airway inflammation in bronchiectasis.This study is funded by UDM Department Research Grants.RM-15RM-16

Differential regulation of cytokine-and phorbol ester-induced activation of nuclear factor kappa B by Pseudomonas aeruginosa pyocyanin in human airway epithelial cells

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Differential regulation of cytokine-and phorbol ester-induced activation of nuclear factor kappa B by Pseudomonas aeruginosa pyocyanin in human airway epithelial cells

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