Differential modulation of interleukin 8 by interleukin 4 and interleukin 10 in HepG2 cells treated with acetaldehyde.
OBJECTIVE
Pro-inflammatory cytokines and chemokines, such as interleukin (IL) 8, are important mediators of hepatic injury and repair following an insult. The purpose of this work was to study the regulation of IL-8 by IL-10 and IL-4 in HepG2 cells treated with acetaldehyde (Ac).


METHODS
HepG2 cells were pretreated with IL-10 or IL-4 before exposure to Ac, examining IL-8 expression by reverse transcription polymerase chain reaction and Western blot.


RESULTS
Ac treatment produced an increment in IL-8 induction and secretion that was prevented by IL-4 pretreatment, while IL-10 pretreatment failed to decrease Ac-induced IL-8 production. Consistent with these findings Ac increased NF-kappa B and AP-1 activation that were prevented by IL-4 but not by IL-10, findings accompanied by greater I kappa B-alpha levels in IL-4 but not IL-10 pretreated cells. In contrast to the pro-inflammatory role of IL-10 in HepG2, IL-10 did not show any change in the activation of NF-kappa B by Ac in WRL-68 cells, a human fetal hepatic cell line. Moreover, IL-10 did not induce the degradation of I kappa B-alpha in cellular extract from rat primary cultured cells.


CONCLUSIONS
While the present findings demonstrate the anti-inflammatory role of IL-4 in preventing the expression of IL-8 by Ac, the regulation of chemokines by anti-inflammatory cytokines is complex and depends on the cellular lineage.
Gómez-Quiroz
Luis Enrique
LE
Experimental Biology PhD Program, Universidad Autonoma Metropolitana-Iztapalapa, Mexico D.F. 09340, Mexico.
Paris
Raquel
R
Lluis
José María
JM
Bucio
Leticia
L
Souza
Verónica
V
Hernández
Elizabeth
E
Gutiérrez
Mario
M
Santiago
Mariana
M
García-Ruiz
Carmen
C
Fernández-Checa
José C
JC
Kershenobich
David
D
Gutiérrez-Ruiz
Ma Concepción
MC
D000079:Acetaldehyde / Q000494:pharmacology*; D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor / Q000187:drug effects / Q000473:pathology; D004338:Drug Combinations; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D016753:Interleukin-10 / Q000494:pharmacology*; D015847:Interleukin-4 / Q000494:pharmacology*; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018808:Transcription Factor AP-1 / Q000378:metabolism
D004338:Drug Combinations; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D016209:Interleukin-8; D016328:NF-kappa B; C000606204:NFKBIA protein, human; C000606206:Nfkbia protein, rat; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D016753:Interleukin-10; D000072000:NF-KappaB Inhibitor alpha; D015847:Interleukin-4; D000079:Acetaldehyde