Expression of proinflammatory cytokines via HIF-1alpha and NF-kappaB activation on desferrioxamine-stimulated HMC-1 cells.
We investigated the expression and the role of hypoxia-inducible factor 1alpha (HIF-1alpha) on the desferrioxamine (DFX)-induced cytokine production in human mast cells, HMC-1 cells. HIF-1alpha mRNA was constitutively expressed in mast cell lines including the P815, RBL-2H3, and HMC-1. DFX (100 microM) resulted in a great increase in protein levels of HIF-1alpha in HMC-1 cells, but it did not affect HIF-1alpha mRNA expression. Iron (HIF-1 inhibitor) inhibited increase of HIF-1alpha and NF-kappaB protein levels. Pyrriolidine-dithiocarbamate (PDTC, NF-kappaB inhibitor) inhibited increase of NF-kappaB protein levels, but it slightly increased HIF-1alpha protein levels. In addition, DFX significantly increased the production of IL-6, IL-8, and TNF-alpha in HMC-1 (P<0.05). These increased cytokine levels were significantly inhibited by treatment of iron or PDTC in a dose-dependent manner (P<0.05). We demonstrated the regulatory effects of HIF-1alpha on the DFX-induced proinflammatory cytokine production in human mast cells for the first time. These data indicate that inflammatory cytokines seem to be under HIF-1alpha or NF-kappaB transcriptional regulation in the hypoxic conditions on mast cells.
Jeong
Hyun-Ja
HJ
Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, 1 Hoegi-Dong, Dongdaemun-Gu, Seoul 130-701, Republic of Korea.
Chung
Hwan-Suck
HS
Lee
Bo-Ra
BR
Kim
Su-Jin
SJ
Yoo
Su-Jin
SJ
Hong
Seung-Heon
SH
Kim
Hyung-Min
HM
D015153:Blotting, Western; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D003676:Deferoxamine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D006801:Humans; D000860:Hypoxia; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007501:Iron / Q000494:pharmacology; D007502:Iron Chelating Agents / Q000494:pharmacology; D008407:Mast Cells / Q000166:cytology; D016328:NF-kappa B / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014157:Transcription Factors / Q000096:biosynthesis*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D016207:Cytokines; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D015850:Interleukin-6; D016209:Interleukin-8; D007502:Iron Chelating Agents; D016328:NF-kappa B; D012333:RNA, Messenger; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007501:Iron; D003676:Deferoxamine