Toll-like receptor and cytokine gene expression in the early phase of human lung transplantation.
BACKGROUND
Innate immunity is the first line of host defense against invading microorganisms, which is mediated by specific pathogen recognition molecules called toll-like receptors (TLRs). TLRs can also recognize endogenous "danger" signals, resulting in cytokine production and activation of the adaptive immune system. We hypothesized that gene expression of TLRs during lung transplantation may be affected by the donor condition and the ischemia-reperfusion process, which may subsequently influence graft function.


METHODS
Lung biopsies from 14 patients were collected before and after reperfusion, and mRNA levels of TLRs, cytokines (interleukin [IL]-1beta, IL-6, IL-8, IL-10 and interferon-gamma) and heat-shock protein 70 (HSP70) were measured by quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR).


RESULTS
In cold-preserved donor lungs, all TLRs (except TLR3) showed significant correlations with one another and also with the cytokines examined. Expression of several TLRs and cytokines correlated with the intubation time of donors. TLR4 gene expression correlated closely with IL-8 before and after reperfusion (p </= 0.01). After reperfusion, HSP70 mRNAs increased significantly (p < 0.05).


CONCLUSIONS
Differential expression levels of TLRs and cytokine genes likely reflect the inflammatory status of lung grafts; correlation of TLR genes with cytokine genes and clinical conditions implicates a potential role of TLRs in early graft responses.
Andrade
Cristiano Feijó
CF
Thoracic Surgery Research Laboratory, Toronto General Hospital, University Health Network, Department of Surgery, University of Toronto, Toronto, Ontario, Canada.
Kaneda
Hiroyuki
H
Der
Sandy
S
Tsang
Melanie
M
Lodyga
Monika
M
Chimisso Dos Santos
Claudia
C
Keshavjee
Shaf
S
Liu
Mingyao
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D001706:Biopsy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics / Q000502:physiology*; D006085:Graft Survival / Q000235:genetics / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051193:Toll-Like Receptors / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D016207:Cytokines; D018840:HSP70 Heat-Shock Proteins; D016209:Interleukin-8; D012333:RNA, Messenger; D051193:Toll-Like Receptors