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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 E 2 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 E 2 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 E 2 and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.Interleukin-18 (IL-18) requires cleavage at its aspartic acid residue by IL-1␤-converting enzyme/caspase-1 to become an active and mature protein (8), and monocytes produce IL-18 while interacting with cognate T cells (10). Furthermore, IL-18 is located upstream of production of Th1 cytokines (8, 12), acts in synergy with IL-12 to induce gamma interferon (IFN-␥) production in CD4 ϩ cells via different signaling pathways (2), and along with IL-12 is necessary for Th1 responses. Cell-tocell interactions brought about via the engagement between intercellular adhesion molecule 1 (ICAM-1), B7.1, B7.2, CD40, and CD40L on monocytes and their ligands on T/NK cells are also involved in the IL-18-induced production of cytokines, including IL-12, tumor necrosis factor alpha (TNF-␣), IFN-␥, and IL-10 (20, 21).A major product of cyclooxygenase (COX)-initiated arachidonic acid metabolism, prostaglandin E 2 (PGE 2 ), which is released from antigen-presenting cells, primes naive human T cells and enhances their production of anti-inflammatory cytokines while inhibiting their synthesis of proinflammatory cytokines (6, 9). Among the four PGE 2 receptor subtypes, Eprostanoid 1 (EP 1 ), EP 2 , EP 3 , and EP 4 , activation of the EP 2 and EP 4 receptors leads to an increase in cyclic AMP (cAMP) levels and protein kinase A (PKA) activity (3). The stimulation of EP 2 receptors directly inhibits T-cell proliferation, while that of EP 2 and EP 4 receptors regulates antigen-presenting cell functions (11). In a previous study, we found that PGE 2 prevented the IL-18-induced expression of ICAM-1, B7.2, and CD40 on monocytes and the production of IL...

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.

The aim of the present study was to demonstrate estrogen receptor (ER) a (ERa ) and ERb expression in the bursa of Fabricius and cultured bursal epithelial cells (CBEC) by reverse transcription (RT)-polymerase chain reaction (PCR) using a primer set design based on the sequences of chicken ERa complementary DNA (cDNA) and chicken ERb -cDNA. In the case of ERa , RT-PCR products of the expected size (698 base pairs (bp)) were amplified from cDNA derived from the bursa and CBEC, and from the oviduct, which was used as a positive control. All of the products were cleaved into two fragments of 476 bp and 222 bp by treating the products with restriction nuclease Hind III, indicating that these RT-PCR products from the bursa, CBEC and genital organs were the same. In contrast, in the case of ERb , PCR products of the expected size (303 bp) were not detected in the bursa of Fabricius or CBEC, or in the oviduct and ovary. These results indicate that ERa is expressed in the bursa of Fabricius and in CBEC, but ERb is not expressed in the bursa or CBEC, or in the female genital organs of chickens.

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