Effect of Ciprofloxacin-Induced Prostaglandin E2 on Interleukin-18-Treated Monocytes

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.

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Effect of trans-10, cis-12 Conjugated Linoleic Acid on Production of Prostaglandin E₂, Cyclooxygenase-2 and 5-lipoxygenase in Lipopolysaccharide-Stimulated Porcine Peripheral Blood Mononuclear Cells

Journal of Veterinary Clinics ◽

10.17555/jvc.2016.08.33.4.194 ◽

2016 ◽

Vol 33 (4) ◽

pp. 194

Author(s):

Hae-Ryun Seo ◽

Changhwan Ahn ◽

Byeong-Teck Kang ◽

Ji-Houn Kang ◽

Eui-Bae Jeung ◽

...

Keyword(s):

Linoleic Acid ◽

Conjugated Linoleic Acid ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Cyclooxygenase 2 ◽

Prostaglandin E ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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Effect of Steroids on Lipopolysaccharide/Interleukin 2-Induced Interleukin 18 Production in Peripheral Blood Mononuclear Cells

Journal of International Medical Research ◽

10.1177/147323000203000207 ◽

2002 ◽

Vol 30 (2) ◽

pp. 144-160 ◽

Cited By ~ 12

Author(s):

M Kodama ◽

HK Takahashi ◽

H Iwagaki ◽

H Itoh ◽

T Morichika ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Steroid Treatment ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Enhanced Production ◽

Blood Mononuclear Cells ◽

Ifn Γ ◽

Cytokine Cascade

Interleukin (IL) 18, a powerful inducer of the immunoregulatory cytokine interferon-γ (IFN-γ), presents upstream of the cytokine activation cascade in the inflammatory response. The anti-inflammatory properties of steroids permit their use in various conditions, although effects are transient and pathological states are not fully relieved by short-term steroidal use. We examined the effect of lipopolysaccharide (LPS)/IL-2 on the cytokine cascade in human peripheral blood mononuclear cells (PBMCs). We also examined the effect of steroids on LPS/IL-2-induced cytokine production in human PBMCs taken from healthy volunteers. Cell-free supernatant fractions were assayed for IL-18, IL-12, IL-2, IFN-γ and IL-10 protein, using enzyme-linked immunosorbent assays, and synergy between LPS and IL-2 in enhanced production of IL-18 was observed. Steroids suppressed the production of IL-18 and other secondary cytokines in LPS/IL-2-stimulated PBMCs, in a concentration- and time-dependent manner, although inhibition was incomplete even at high concentrations. Effects of steroid treatment on expression of membrane-bound LPS receptor antigen (mCD14) and intercellular adhesion molecule-1 (ICAM-1) in PBMCs were studied by flow cytometric analysis. Steroid treatment up-regulated mCD14 expression in a concentration-dependent manner, with no effect on ICAM-1 expression. These results suggest that the incomplete counteraction of steroids in the LPS/IL-2-initiating cytokine cascade is due, at least partly, to the up-regulation of mCD14 by steroid preparations, which increases susceptibility to bacterial endotoxins.

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Modulation by thymus-derived (T) cells of thyroid cell-stimulated prostaglandin E release by human peripheral blood mononuclear cells.

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.76.12.6627 ◽

1979 ◽

Vol 76 (12) ◽

pp. 6627-6631 ◽

Cited By ~ 4

Author(s):

M. Yamamoto ◽

N. A. Takai ◽

B. Rapoport ◽

W. E. Hinds

Keyword(s):

T Cells ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Prostaglandin E ◽

Thyroid Cell ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Prostaglandin E Release

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Leishmania (Viannia) braziliensis amastigotes induces the expression of TNFα and IL-10 by human peripheral blood mononuclear cells in vitro in a TLR4-dependent manner

Cytokine ◽

10.1016/j.cyto.2016.09.009 ◽

2016 ◽

Vol 88 ◽

pp. 184-192 ◽

Cited By ~ 13

Author(s):

Hélio Galdino ◽

Rodrigo Saar Gomes ◽

Jessica Cristina dos Santos ◽

Lívia Lara Pessoni ◽

Anetícia Eduarda Maldaner ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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Atopic Dermatitis in Adults: Evaluation of Peripheral Blood Mononuclear Cells Proliferation Response to Staphylococcus aureus Enterotoxins A and B and Analysis of Interleukin-18 Secretion

Dermatitis ◽

10.1097/01206501-200807000-00042 ◽

2008 ◽

Vol 19 (4) ◽

pp. 218-238

Author(s):

R. L. Orfali ◽

M. N. Sato ◽

R. Takaoka ◽

A. J. S. Duarte ◽

E. A. Rivitti ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Atopic Dermatitis ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Interleukin 18 ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells ◽

Proliferation Response ◽

Staphylococcus Aureus Enterotoxins

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Increased expression of allergen-induced in vitro interleukin-10 and interleukin-18 mRNA in peripheral blood mononuclear cells of allergic rhinitis patients after specific immunotherapy

Clinical & Experimental Allergy ◽

10.1111/j.1365-2222.2004.01823.x ◽

2004 ◽

Vol 34 (3) ◽

pp. 413-419 ◽

Cited By ~ 33

Author(s):

J. Savolainen ◽

K. Laaksonen ◽

A. Rantio-Lehtimaki ◽

E.O. Terho

Keyword(s):

Allergic Rhinitis ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Specific Immunotherapy ◽

Mononuclear Cells ◽

Interleukin 10 ◽

Interleukin 18 ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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HMG-CoA reductase inhibition induces IL-1β release through Rac1/PI3K/PKB-dependent caspase-1 activation

Blood ◽

10.1182/blood-2008-03-144667 ◽

2008 ◽

Vol 112 (9) ◽

pp. 3563-3573 ◽

Cited By ~ 95

Author(s):

Loes M. Kuijk ◽

Jeffrey M. Beekman ◽

Janet Koster ◽

Hans R. Waterham ◽

Joost Frenkel ◽

...

Keyword(s):

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Isoprenoid Biosynthesis ◽

Dependent Manner ◽

Peripheral Blood Mononuclear ◽

Simvastatin Treatment ◽

Caspase 1 ◽

Blood Mononuclear Cells ◽

Coa Reductase

Mevalonate kinase deficiency (MKD) is an autoinflammatory disorder characterized by recurring fever episodes and results from disturbed isoprenoid biosynthesis. Lipopolysaccharide-stimulated peripheral blood mononuclear cells from MKD patients secrete high levels of interleukin-1β (IL-1β) because of the presence of hyperactive caspase-1, and this has been proposed to be the primary cause of recurring inflammation. Here we show that inhibition of HMG-CoA reductase by simvastatin treatment, mimicking MKD, results in increased IL-1β secretion in a Rac1/PI3K-dependent manner. Simvastatin treatment was found to activate protein kinase B (PKB)/c-akt, a primary effector of PI3K, and ectopic expression of constitutively active PKB was sufficient to induce IL-1β release. The small GTPase Rac1 was activated by simvastatin, and this was required for both PKB activation and IL-1β secretion. IL-1β release is mediated by caspase-1, and simvastatin treatment resulted in increased caspase-1 activity in a Rac1/PI3K-dependent manner. These data suggest that, in MKD, dysregulated isoprenoid biosynthesis activates Rac1/PI3K/PKB, resulting in caspase-1 activation with increased IL-1β release. Importantly, inhibition of Rac1 in peripheral blood mononuclear cells isolated from MKD patients resulted in a dramatic reduction in IL-1β release. These data suggest that pharmacologic inhibition of Rac1 could provide a novel therapeutic strategy for treatment of MKD.

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