The effect of ciprofloxacin on CD14 and toll-like receptor-4 expression on human monocytes.
CD14/toll-like receptor (TLR)-4 complex on monocytes/macrophages can bind lipopolysaccharide (LPS) and transduce the signals intracellularly. An antibacterial drug, ciprofloxacin (CIP), has been reported to modulate the inflammatory and immune responses. In the present study, we examined the effects of CIP on the LPS-induced activation of monocytes isolated from human peripheral blood mononuclear cells (PBMC). CIP suppressed the expression of CD14, TLR-4, intercellular adhesion molecule (ICAM)-1, B7.1, B7.2, and CD40 and the production of tumor necrosis factor (TNF)-alpha induced by LPS in monocytes. CIP induced the production of prostaglandin (PG)E2 and increased intracellular cyclic adenosine monophosphate (cAMP) levels. Cyclooxygenase (COX)-2 inhibitors, NS398 and indomethacin, reversed the effects of CIP on TNF-alpha production and reduced the levels of different surface antigens, whereas a protein kinase A (PKA) inhibitor, H89, did not. Therefore, CIP might regulate the TNF-alpha production induced by LPS by inhibiting the expression of LPS receptor complex, which seems to be mediated by COX-2 but not the cAMP/PKA pathway.
Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Goutaro
G
Katsuno
Hideo Kohka
HK
Takahashi
Hiromi
H
Iwagaki
Sachi
S
Sugita
Shuji
S
Mori
Shinnya
S
Saito
Tadashi
T
Yoshino
Masahiro
M
Nishibori
Noriaki
N
Tanaka
D015703:Antigens, CD / Q000097:blood; D002939:Ciprofloxacin / Q000494:pharmacology*; D015232:Dinoprostone / Q000097:blood; D006801:Humans; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000097:blood / Q000187:drug effects; D007700:Kinetics; D018950:Lipopolysaccharide Receptors / Q000097:blood* / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D009000:Monocytes / Q000187:drug effects / Q000502:physiology*; D051197:Toll-Like Receptor 4 / Q000097:blood* / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000378:metabolism
D015703:Antigens, CD; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D002939:Ciprofloxacin; D015232:Dinoprostone; D007213:Indomethacin