Reduced hepatic ischemia/reperfusion injury by IL-4: potential anti-inflammatory role of STAT6.
OBJECTIVE
The ability of interleukin-4 (IL-4) to modulate activation of the transcription factors, NF-kappaB and STAT6, reduce proinflammatory cytokine expression and protect against liver injury induced by ischemia/reperfusion was assessed.


METHODS
C57BL/6 mice underwent 90 minutes of partial hepatic ischemia followed by 1 or 8 h of reperfusion with or without intravenous administration of 1 microg (0.5 microg just prior to ischemia, 0.5 microg at reperfusion) recombinant murine IL-4. Liver expression of TNFalpha mRNA was determined by RT-PCR. Activation of NF-kappaB and STAT6 in liver nuclear extracts was assessed by mobility shift assay.


RESULTS
Hepatic ischemia/reperfusion increased hepatic expression of tumor necrosis factor-alpha (TNFalpha), induced significant neutrophil accumulation and liver injury. Treatment with IL-4 greatly suppressed liver TNFalpha mRNA expression, neutrophil accumulation and liver injury. IL-4 had no effect on liver NF-kappaB activation, but greatly increased the activation of STAT6.


CONCLUSIONS
The data suggest that STAT6 activation by IL-4 may be responsible for the protective effects of this cytokine.
Department of Surgery, University of Louisville School of Medicine, J. G. Brown Cancer Center, Kentucky 40202, USA.
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Kato
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Yoshidome
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MJ
Edwards
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AB
Lentsch
D000818:Animals; D007249:Inflammation / Q000517:prevention & control*; D015847:Interleukin-4 / Q000494:pharmacology*; D007511:Ischemia / Q000188:drug therapy*; D008099:Liver / Q000098:blood supply*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D015427:Reperfusion Injury / Q000517:prevention & control*; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D016328:NF-kappa B; D012333:RNA, Messenger; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; D015534:Trans-Activators; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4