Premium
Comparison of suppressive effects of a new anti‐inflammatory compound, FR167653, on production of PGE 2 and inflammatory cytokines, human monocytes, and alveolar macrophages in response to endotoxin
Author(s) -
Kawano Tetsuya,
Ogushi Fumitaka,
Tani Kenji,
Endo Takeshi,
Ohmoto Yasukazu,
Hayashi Yoko,
Sone Saburo
Publication year - 1999
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.65.1.80
Subject(s) - proinflammatory cytokine , cytokine , cyclooxygenase , lipopolysaccharide , prostaglandin e2 , interleukin , immunology , tumor necrosis factor alpha , monocyte , medicine , pharmacology , inflammation , biology , biochemistry , enzyme
FR167653 {1‐[7‐(4‐fluorophenyl)‐1, 2, 3, 4‐tetrahydro‐8 (4‐pyridyl) pyrazoro [5‐1‐c] [1, 2, 4] triazin‐2‐ yl ]‐2‐phenylethanedion sulfate monohydrate} was developed to inhibit proinflammatory cytokine production. However, the effects of FR167653 on prostanoid production are unclear. We investigated the effect of FR167653 on proinflammatory cytokine and prostaglandin (PG) production by lipopolysaccharide (LPS)‐stimulated human peripheral blood monocytes and alveolar macrophages (AM) from the same individuals, and compared the effects in monocytes and AM. FR167653 inhibited interleukin‐1β and tumor necrosis factor a production. The effect on PGE 2 production was assessed by four parameters. FR167653 inhibited PGE 2 synthesis and LPS induction of cyclooxygenase activity. Western and Northern blot analyses revealed that LPS induction of cyclooxygenase‐2 expression was attenuated by this compound. The suppression in monocytes was greater than that in AM. We concluded that the reduction of LPS‐induced PGE 2 synthesis by FR167653 was due to inhibition of cyclooxygenase‐2 production. These results show that FR167653 may be therapeutically useful for inhibiting production of both inflammatory cytokines and PG production in inflammatory diseases. J. Leukoc. Biol. 65: 80–86; 1999.