Abstract
Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E2 in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E2 and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E2 and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.
| Original language | English |
|---|---|
| Pages (from-to) | 3228-3233 |
| Number of pages | 6 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 49 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2005 |
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ASJC Scopus subject areas
- Pharmacology (medical)
Cite this
Effect of ciprofloxacin-induced prostaglandin E2 on interleukin-18-treated monocytes. / Takahashi, Hideo Kohka; Iwagaki, Hiromi; Xue, Dong; Katsuno, Goutarou; Sugita, Sachi; Mizuno, Kenji; Mori, Shuji; Saito, Shinya; Yoshino, Tadashi; Tanaka, Noriaki; Nishibori, Masahiro.
In: Antimicrobial Agents and Chemotherapy, Vol. 49, No. 8, 08.2005, p. 3228-3233.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of ciprofloxacin-induced prostaglandin E2 on interleukin-18-treated monocytes
AU - Takahashi, Hideo Kohka
AU - Iwagaki, Hiromi
AU - Xue, Dong
AU - Katsuno, Goutarou
AU - Sugita, Sachi
AU - Mizuno, Kenji
AU - Mori, Shuji
AU - Saito, Shinya
AU - Yoshino, Tadashi
AU - Tanaka, Noriaki
AU - Nishibori, Masahiro
PY - 2005/8
Y1 - 2005/8
N2 - Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E2 in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E2 and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E2 and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.
AB - Ciprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E2 in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E2 and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E2 and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.
UR - http://www.scopus.com/inward/record.url?scp=23044462517&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23044462517&partnerID=8YFLogxK
U2 - 10.1128/AAC.49.8.3228-3233.2005
DO - 10.1128/AAC.49.8.3228-3233.2005
M3 - Article
C2 - 16048930
AN - SCOPUS:23044462517
VL - 49
SP - 3228
EP - 3233
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 8
ER -