Background and Purpose Advanced glycation end products (AGEs) subtypes, proteins or lipids that become glycated after exposure to sugars, can induce complications in diabetes. Among the various AGE subtypes, glyceraldehyde- derived AGE (AGE-2) and glycolaldehyde-derived AGE (AGE-3) are involved in inflammation in diabetic patients; monocytes are activated by these AGEs. Ciprofloxacin (CIP), a fluorinated 4-quinolone, is often used clinically to treat infections associated with diabetis due to its antibacterial properties. It also modulates immune responses in human peripheral blood mononuclear cells (PBMC) therefore we investigated the involvement of AGEs in these effects. Experimental Approach Expression of intercellular adhesion molecule (ICAM)-1, B7.1, B7.2 and CD40 was examined by flow cytometry. The production of tumour necrosis factor (TNF)-α, interferon (IFN)-γ, prostaglandin E 2 (PGE 2) and cAMP were determined by enzyme-linked immunosorbent assay. Cyclooxygenase (COX)-2 expression was determined by Western blot analysis. Lymphocyte proliferation was determined by [ 3H]- thymidine uptake. Key Results CIP induced PGE 2 production in monocytes, irrespective of the presence of AGE-2 and AGE-3, by enhancing COX-2 expression; this led to an elevation of intracellular cAMP in monocytes. Non-selective and selective COX-2 inhibitors, indomethacin and NS398, inhibited CIP-induced PGE 2 and cAMP production. In addition, CIP inhibited AGE-2- and AGE-3-induced expressions of ICAM-1, B7.1, B7.2 and CD40 in monocytes, the production of TNF-α and IFN-γ and lymphocyte proliferation in PBMC. Indomethacin, NS398 and a protein kinase A inhibitor, H89, inhibited the actions of CIP. Conclusions and Implications CIP exerts immunomodulatory activity via PGE 2, implying therapeutic potential of CIP for the treatment of AGE-2- and AGE-3-induced inflammatory responses.
- adhesion molecule
- advanced glycation end products
- cyclic adenosine monophosphate
- peripheral blood mononuclear cells
- prostaglandins E2
- protein kinase A
ASJC Scopus subject areas