Induction of release and up-regulated gene expression of interleukin (IL)-8 in A549 cells by serine proteinases.
BACKGROUND
Hypersecretion of cytokines and serine proteinases has been observed in asthma. Since protease-activated receptors (PARs) are receptors of several serine proteinases and airway epithelial cells are a major source of cytokines, the influence of serine proteinases and PARs on interleukin (IL)-8 secretion and gene expression in cultured A549 cells was examined.


RESULTS
A549 cells express all four PARs at both protein and mRNA levels as assessed by flow cytometry, immunofluorescence microscopy and reverse transcription polymerase chain reaction (PCR). Thrombin, tryptase, elastase and trypsin induce a up to 8, 4.3, 4.4 and 5.1 fold increase in IL-8 release from A549 cells, respectively following 16 h incubation period. The thrombin, elastase and trypsin induced secretion of IL-8 can be abolished by their specific inhibitors. Agonist peptides of PAR-1, PAR-2 and PAR-4 stimulate up to 15.6, 6.6 and 3.5 fold increase in IL-8 secretion, respectively. Real time PCR shows that IL-8 mRNA is up-regulated by the serine proteinases tested and by agonist peptides of PAR-1 and PAR-2.


CONCLUSIONS
The proteinases, possibly through activation of PARs can stimulate IL-8 release from A549 cells, suggesting that they are likely to contribute to IL-8 related airway inflammatory disorders in man.
Wang
Haiyan
H
Allergy and Inflammation Research Institute, the Key Immunopharmacology Laboratory of Guangdong Province, Shantou University Medical College, Shantou 515031, China.
Zheng
Yanshan
Y
He
Shaoheng
S
D045744:Cell Line, Tumor; D005786:Gene Expression Regulation; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D008168:Lung / Q000276:immunology* / Q000378:metabolism; D010196:Pancreatic Elastase / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D044462:Receptors, Proteinase-Activated / Q000819:agonists / Q000378:metabolism; D012697:Serine Endopeptidases / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014357:Trypsin / Q000494:pharmacology; D053802:Tryptases; D015854:Up-Regulation
D016209:Interleukin-8; D012333:RNA, Messenger; D044462:Receptors, Proteinase-Activated; D015842:Serine Proteinase Inhibitors; D012697:Serine Endopeptidases; D010196:Pancreatic Elastase; D014357:Trypsin; D013917:Thrombin; D053802:Tryptases