Involvement of cystic fibrosis transmembrane conductance regulator in infection-induced edema.
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.
Ajonuma
Louis Chukwuemeka
LC
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.
He
Qiong
Q
Sheung Chan
Paul Kay
PK
Yu Ng
Ernest Hung
EH
Fok
Kin Lam
KL
Yan Wong
Connie Hau
CH
Tsang
Lai Ling
LL
Ho
Lok Sze
LS
Lau
Miu Ching
MC
Huang
Hong Yi
HY
Yang
Dong Zi
DZ
Rowlands
Dewi Kenneth
DK
Tang
Xiao Xiao
XX
Zhang
Xiao Hu
XH
Chung
Yiu Wa
YW
Chan
Hsiao Chang
HC
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
D016207:Cytokines; D053583:Interleukin-1beta; D019005:Cystic Fibrosis Transmembrane Conductance Regulator