[Effects of erythromycin on the synthesis of interleukin-8 and gamma-glutamylcysteine synthetase induced by 4-hydroxynonenal in the bronchial epithelial cells].
OBJECTIVE
This study was to explore the role of erythromycin on the synthesis of interleukin-8 (IL-8) and gamma-GCS treated by 4-hydroxynonenal (4-HNE) in bronchial epithelial cells (16-HBE).


METHODS
(1) The experiment groups were divided into 10 micromol/L 4-HNE and control groups. The phosphorylation of ERK-1, JNK, P38MAPK and the combining activity of AP-1 after 10 micromol/L 4-HNE stimulating for 0.5, 2, 4, 8, 12 hours were all estimated. (2) The IL-8 and IL-8 mRNA, gamma-GCS and gamma-GCS mRNA were measured after 4-HNE (or serum-free medium) stimulating 0.5, 2, 4, 8, 12 hours. (3) The effects of PD98059 and erythromycin on the expression of gamma-GCS, gamma-GCS mRNA, IL-8 and erythromycin on AP-1 combining activity by the 4-HNE were all detected.


RESULTS
(1) The level of phosphorylation of ERK1 in the 4-HNE and control groups were 110.4+/-1.6, 114.6+/-2.4, 106.1+/-2.1, 110.2+/-2.0, 104.4+/-3.4, 112.8+/-2.4, 96.3+/-9.6, 115.4+/-3.8, 86.3+/-2.8, 113.1+/-2.6 at 0.5, 2, 4, 8, 12 hours, respectively, P<0.05. While the AP-1 combining activity in the 4-HNE and control groups were 90.6+/-2.0, 98.6+/-2.1, 85.7+/-2.2, 98.7+/-3.4, 78.2+/-2.6, 100.1+/-3.8, 70.6+/-1.8, 101.3+/-4.2, 64.9+/-4.8, 97.4+/-3.6, respectively P<0.05. (2) The level of IL-8 in the 4-HNE and control groups at 2, 4, 8, 12 hours were (87.4+/-3.8) microg/L, (63.9+/-3.8) microg/L, (98.3+/-4.2) microg/L, (65.3+/-6.2) microg/L, (102.4+/-5.7) microg/L, (64.6+/-4.8) microg/L, (116.5+/-5.6) microg/L, (63.7+/-6.6) microg/L, respectively, P<0.05. The levels of gamma-GCS at 2, 4, 8, 12 hours in two groups were 5.43+/-0.23, 4.78+/-0.26, 5.41+/-0.27, 4.03+/-0.34, 5.54+/-0.53, 3.22+/-0.31, respectively, P<0.05. IL-8 mRNA, gamma-GCS mRNA after 4-HNE stimulation were all increased compared with the control groups. (3) The expression of IL-8 and AP-1 combining activity was decreased, but synthesis of gamma-GCS was increased after treatment with PD98059 or erythromycin before treated with 4-HNE.


CONCLUSIONS
4-HNE could increase the expression of IL-8 in the bronchial epithelial cells, via increasing the transcribing activities of AP-1 via ERK-1 cell signal transduction ways. Erythromycin could inhibit the synthesis of IL-8 by blocking AP-1 pathway. PD98059 and erythromycin could block AP-1 transduction pathway, but increase the synthesis of gamma-GCS induced by 4-HNE in bronchial epithelial cells.
Yu
Liang
L
Guangzhou Institute of Respiratory Disease, the First Affiliated Hospital of Guangzhou Medical College, Guangzhou 510182, China.
Ran
Pei-xin
PX
D000447:Aldehydes / Q000494:pharmacology*; D001980:Bronchi / Q000166:cytology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism*; D004917:Erythromycin / Q000494:pharmacology*; D005419:Flavonoids / Q000494:pharmacology; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis*; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000447:Aldehydes; C508606:CXCL8 protein, human; D005419:Flavonoids; D016209:Interleukin-8; D018808:Transcription Factor AP-1; D004917:Erythromycin; D005721:Glutamate-Cysteine Ligase; C027576:4-hydroxy-2-nonenal; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one