Human placenta promotes IL-8 expression through activation of JNK/SAPK and transcription factors NF-kappaB and AP-1 in PMA-differentiated THP-1 cells.
Human placenta is a rich reservoir of diverse bioactive molecules with therapeutic potential against certain diseases such as immune disorders. In the present study, we investigated the ability of human placenta extract (HPE) to induce expression of a CXC chemokine, interleukin-8 (IL-8), in a human monocytic cell line, THP-1, differentiated into macrophages with phorbol 12-myristate 13-acetate (PMA). HPE significantly induced IL-8 mRNA and protein expressions in a dose-dependent manner. HPE-induced IL-8 expression was inhibited by a selective inhibitor of JNK/SAPK, but not by inhibitors of p38 kinase or ERK. Since IL-8 transcription is known to be regulated by nuclear factor (NF)-kappaB, activating protein (AP)-1 and NF for IL-6 (NF-IL6), an electrophoretic mobility shift assay was performed to examine the DNA-binding activities of these transcription factors. The DNA-binding activities of NF-kappaB and AP-1 increased in cells treated with HPE in a dose-dependent manner, while no change was observed in NF-IL6 binding activity under the same conditions. Taken together, these results suggest that HPE-induced IL-8 secretion occurs via activation of JNK/SAPK and transcription factors NF-kappaB and AP-1 in PMA-differentiated THP-1 cells.
Kang
Seok-Seong
SS
Department of Oral Microbiology & Immunology, Dental Research Institute, and BK21 Program, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea.
Woo
Sang Su
SS
Im
Jintaek
J
Yang
Jae Seung
JS
Yun
Cheol-Heui
CH
Ju
Hyang Ran
HR
Son
Chang Gue
CG
Moon
Eun-Yi
EY
Han
Seung Hyun
SH
D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics* / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism*; D048055:Mitogen-Activated Protein Kinase 8 / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism*; D010920:Placenta / Q000378:metabolism*; D010924:Placental Extracts / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000378:metabolism*
D022782:CCAAT-Enhancer-Binding Protein-beta; D016209:Interleukin-8; D016328:NF-kappa B; D010924:Placental Extracts; D012333:RNA, Messenger; D018808:Transcription Factor AP-1; D048055:Mitogen-Activated Protein Kinase 8; D048670:MAP Kinase Kinase 4; D013755:Tetradecanoylphorbol Acetate