title: Involvement of cystic fibrosis transmembrane conductance regulator in infection-induced edema.
abstract: Abnormal fluid accumulation in tissues, including the life-threatening cerebral and pulmonary edema, is a severe consequence of bacteria infection. Chlamydia (C.) trachomatis is an obligate intracellular gram-negative human pathogen responsible for a spectrum of diseases, causing tissue fluid accumulation and edema in various organs. However, the underlying mechanism for tissue fluid secretion induced by C. trachomatis and most of other infectious pathogens is not known. Here, we report that in mice C. trachomatis infection models, the expression of cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP activated chloride channel, is up regulated together with increased cytokine release and tissue fluid accumulation that can be reversed by treatment with antibiotic specific for C. trachomatis and CFTR channel blocker. However, C. trachomatis infection cannot induce tissue edema in CFTRtm1Unc mutant mice. Administration of exogenous IL-1beta to mice mimics the C. trachomatis infection-induced CFTR upregulation, enhanced CFTR channel activity and fluid accumulation, further confirming the involvement of CFTR in infection-induced tissue fluid secretion.
authors.affiliation: Epithelial Cell Biology Research Center, Li Ka Shing Institute of Health Science, Department of Physiology, The Chinese University of Hong Kong, Shatin, NT, Hong Kong.
authors.forename: Louis Chukwuemeka
authors.initials: LC
authors.lastname: Ajonuma
authors.forename: Qiong
authors.initials: Q
authors.lastname: He
authors.forename: Paul Kay
authors.initials: PK
authors.lastname: Sheung Chan
authors.forename: Ernest Hung
authors.initials: EH
authors.lastname: Yu Ng
authors.forename: Kin Lam
authors.initials: KL
authors.lastname: Fok
authors.forename: Connie Hau
authors.initials: CH
authors.lastname: Yan Wong
authors.forename: Lai Ling
authors.initials: LL
authors.lastname: Tsang
authors.forename: Lok Sze
authors.initials: LS
authors.lastname: Ho
authors.forename: Miu Ching
authors.initials: MC
authors.lastname: Lau
authors.forename: Hong Yi
authors.initials: HY
authors.lastname: Huang
authors.forename: Dong Zi
authors.initials: DZ
authors.lastname: Yang
authors.forename: Dewi Kenneth
authors.initials: DK
authors.lastname: Rowlands
authors.forename: Xiao Xiao
authors.initials: XX
authors.lastname: Tang
authors.forename: Xiao Hu
authors.initials: XH
authors.lastname: Zhang
authors.forename: Yiu Wa
authors.initials: YW
authors.lastname: Chung
authors.forename: Hsiao Chang
authors.initials: HC
authors.lastname: Chan
mesh_terms: D000818:Animals; D001927:Brain Diseases / Q000378:metabolism; D001929:Brain Edema / Q000209:etiology / Q000378:metabolism; D020806:Central Nervous System Bacterial Infections / Q000378:metabolism; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology; D002692:Chlamydia trachomatis / Q000378:metabolism; D003550:Cystic Fibrosis / Q000378:metabolism; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004487:Edema / Q000209:etiology / Q000378:metabolism*; D005260:Female; D053583:Interleukin-1beta / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D018181:Mice, Inbred CFTR; D015854:Up-Regulation; D014591:Uterine Diseases / Q000378:metabolism
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D019005:Cystic Fibrosis Transmembrane Conductance Regulator