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Published on: June 26, 2018
The effect of ciprofloxacin on CD14 and toll-like receptor-4 expression on human monocytes
Goutaro Katsuno1, Hideo Kohka Takahashi, Hiromi Iwagaki
1Department of Gastroenterological Surgery, Transplant, and Surgical Oncology, Okayama University Graduate School of Medicine and Dentistry, 2-5-1 Shikata-cho, Okayama 700-8558, Japan.
Abstract:
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.
Insights
Ciprofloxacin (CIP) reduces lipopolysaccharide (LPS)-induced monocyte activation by downregulating the CD14/toll-like receptor-4 complex. This immune modulation appears mediated by cyclooxygenase-2, not the cAMP/protein kinase A pathway.
Area of Science:
- Immunology
- Pharmacology
Background:
- The CD14/toll-like receptor (TLR)-4 complex on monocytes/macrophages binds lipopolysaccharide (LPS), initiating intracellular signaling.
- Ciprofloxacin (CIP), an antibacterial drug, is known to modulate inflammatory and immune responses.
Purpose of the Study:
- To investigate the effects of CIP on LPS-induced activation of human peripheral blood mononuclear cell (PBMC)-derived monocytes.
- To elucidate the molecular mechanisms underlying CIP's immunomodulatory effects.
Main Methods:
- Monocytes were isolated from human PBMCs.
- Cells were treated with LPS and varying concentrations of CIP.
- Expression of surface markers (CD14, TLR-4, ICAM-1, B7.1, B7.2, CD40) and production of tumor necrosis factor (TNF)-alpha were assessed.
- Prostaglandin E2 (PGE2) and cyclic adenosine monophosphate (cAMP) levels were measured.
- Inhibitors of cyclooxygenase-2 (COX-2) and protein kinase A (PKA) were used to probe signaling pathways.
Main Results:
- CIP suppressed LPS-induced expression of CD14, TLR-4, ICAM-1, B7.1, B7.2, and CD40 on monocytes.
- CIP inhibited LPS-induced TNF-alpha production.
- CIP increased PGE2 production and intracellular cAMP levels.
- COX-2 inhibitors reversed CIP's effects on TNF-alpha and surface antigen expression, while a PKA inhibitor did not.
Conclusions:
- CIP regulates LPS-induced TNF-alpha production by inhibiting the LPS receptor complex expression.
- This regulation appears to be mediated by the COX-2 pathway.
- The cAMP/PKA pathway is not involved in CIP's observed immunomodulatory effects on TNF-alpha production.
