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Simultaneous induction of matrix metalloproteinase‐9 and interleukin 8 by all‐ trans retinoic acid in human PL‐21 and NB4 myeloid leukaemia cells
Author(s) -
Shibakura Misako,
Niiya Kenji,
Kiguchi Toru,
Shinagawa Katsuji,
Ishimaru Fumihiko,
Ikeda Kazuma,
Namba Masayoshi,
Nakata Yasunari,
Harada Mine,
Tanimoto Mitsune
Publication year - 2002
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2002.03723.x
Subject(s) - retinoic acid , myeloid , cell culture , microbiology and biotechnology , biology , immunology , tretinoin , u937 cell , chemokine , matrix metalloproteinase , cancer research , chemistry , inflammation , biochemistry , genetics
Summary. All‐ trans retinoic acid (ATRA) has been shown to induce differentiation of human acute promyelocytic leukaemia (APL) cells and eventual elimination of the malignant clone. Matrix metalloproteinase‐9 (MMP‐9) is produced by neutrophils and its expression appears to be linked with myeloid cell differentiation. We investigated effects of ATRA on MMP expression in two human myeloid leukaemia cell lines, PL‐21 and NB4. Both cells could differentiate into neutrophils after exposure to ATRA. Both the activity and antigen levels of MMP‐9 were much higher in NB4 cells than in PL‐21 cells. Stimulation with ATRA significantly increased MMP‐9 levels approximately three‐ to fivefold in both PL‐21 and NB4‐conditioned media. MMP‐9 mRNA levels increased in ATRA‐treated cells and was almost in parallel with the increase in MMP‐9 activity, suggesting that ATRA induced MMP‐9 by activating its gene expression. ATRA can induce interleukin 8 (IL‐8) in APL cells. IL‐8, chemokine for neutrophils and a potent inducer of MMP‐9, was also induced by ATRA in PL‐21 cells. However, recombinant IL‐8 did not induce MMP‐9 expression. In addition, a neutralizing antibody against IL‐8 did not inhibit ATRA‐induced MMP‐9 expression in either cell type. These observations suggest that ATRA can induce both MMP‐9 and IL‐8, but IL‐8 is not involved in ATRA‐induced MMP‐9 expression. As MMP‐9 can truncate and activate IL‐8, simultaneous induction of MMP‐9 and IL‐8 by ATRA could activate leucocytes excessively, causing the hyper‐inflammatory events in retinoic acid syndrome.