Cysteinyl leukotrienes induce macrophage inflammatory protein-1 in human monocytes/macrophages.
BACKGROUND
Macrophage inflammatory protein-1alpha (MIP-1alpha) and MIP-1beta are known for their chemotactic and proinflammatory effects on monocytes/macrophages which have a cysteinyl leukotriene 1 (CysLT(1)) receptor.


METHODS
We examined MIP-1alpha and MIP-1beta production stimulated by CysLTs (LTC(4), LTD(4), and LTE(4)) in THP-1 cells, a human monocytic leukemia cell line, and peripheral blood mononuclear cells (PBMCs). Moreover, we examined the inhibitory effect of pranlukast, a CysLT(1) receptor antagonist, and inhibitors of three major mitogen-activated protein kinases (MAPK) on the induction of MIP-1alpha and MIP-1beta production by CysLTs.


RESULTS
ELISA demonstrated that CysLTs induced MIP-1alpha and MIP-1beta production in THP-1 cells and PBMCs. PCR demonstrated that LTD(4) increased MIP-1alpha and MIP-1beta mRNA expressions in THP-1 cells. Pranlukast blocked MIP-1alpha and MIP-1beta production promoted by LTD(4) in THP-1 cells and PBMCs. Moreover, an inhibitor of extracellular signal-regulated kinase (ERK) attenuated the induction of MIP-1alpha and MIP-1beta production by LTD(4) in THP-1 cells whereas the inhibitors of c-Jun NH2-terminal kinase or p38 MAPK did not.


CONCLUSIONS
CysLTs induce MIP-1alpha and MIP-1beta production mediated by ERK via binding to the CysLT(1) receptor in human monocytes/macrophages.
Ichiyama
Takashi
T
Department of Pediatrics, Yamaguchi University Graduate School of Medicine, Yamaguchi, Japan. ichiyama@yamaguchi-u.ac.jp
Hasegawa
Masanari
M
Hashimoto
Kunio
K
Matsushige
Takeshi
T
Hirano
Reiji
R
Furukawa
Susumu
S
D002460:Cell Line; D054405:Chemokine CCL3 / Q000187:drug effects / Q000378:metabolism*; D054407:Chemokine CCL4 / Q000187:drug effects / Q000378:metabolism*; D003545:Cysteine / Q000494:pharmacology*; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D015289:Leukotrienes / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism*
D054405:Chemokine CCL3; D054407:Chemokine CCL4; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D019950:Mitogen-Activated Protein Kinase 1; D003545:Cysteine