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. 1995 Oct;116(4):2298–2302. doi: 10.1111/j.1476-5381.1995.tb15068.x

The effect of a synthetic 7-thiaprostaglandin E1 derivative, TEI-6122, on monocyte chemoattractant protein-1 induced chemotaxis in THP-1 cells.

H Tanaka 1, T Minoshima 1, N Endo 1
PMCID: PMC1908987  PMID: 8564263

Abstract

1 The ability of various prostaglandins (PGs) to inhibit monocyte chemotaxis induced by monocyte chemoattractant protein-1 (MCP-1) was investigated with a human monocytic leukaemia cell line, THP-1. Moreover, to investigate the mechanism of the inhibitory action of PGs the involvement of either intracellular adenosine 3': 5'-cyclic monosphosphate (cyclic AMP) accumulation or intracellular Ca2+ mobilization was studied. 2 TEI-6122, a synthetic 7-thia-PGE1 derivative, inhibited chemotaxis of THP-1 cells induced by MCP-1 with an IC50 of 1.5 pM. Its inhibitory activity was 1000 fold more than that of PGE1 and PGE2 (IC50 = 2.8 nM and 0.9 nM, respectively), which were more potent than other PGs such as PGA1, PGA2, PGF2 alpha and PGI2 (IC50 > or = 1 microM). 3 With respect to the effect on intracellular cyclic AMP accumulation in THP-1 cells, TEI-6122 was as potent as PGE1 and PGE2, which were approximately 100 to 1000 fold more potent than the other PGs such as PGA1, PGA2 and PGI2. The minimum concentration of TEI-6122 required to increase intracellular cyclic AMP accumulation in THP-1 cells was 1 nM. 4 TEI-6122 and PGE1 (4 microM) transiently increased intracellular calcium levels in THP-1 cells. When added prior to MCP-1, both PGs partially suppressed the increased in Ca2+ caused by this cytokine. There were no significant differences between the activity of TEI-6122 and PGE1 in either respect.(ABSTRACT TRUNCATED AT 250 WORDS)

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Selected References

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