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Pro-atherogenic properties of lipopolysaccharide from the periodontal pathogen Actinobacillus actinomycetemcomitans

Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland

Markku Lehto

Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland

Anita M. Tuomainen

Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland

Matti Jauhiainen

Department of Molecular Medicine, National Public Health Institute, Helsinki, Finland

Ernst Malle

Institute of Molecular Biology and Biochemistry, Center of Molecular Medicine, Medical University Graz, Graz, Austria

Sirkka Asikainen

Section of Oral Microbiology, Institute of Odontology, UmeÅ University, UmeÅ, Sweden

Pirkko J. Pussinen

Institute of Dentistry, University of Helsinki, and Department of Oral and Maxillofacial Diseases, Helsinki University Central Hospital, Helsinki, Finland, pirkko.pussinen{at}helsinki.fi

An association between cardiovascular and periodontal disease may be due to lipopolysaccharide (LPS)-promoted release of inflammatory mediators, adverse alterations of the lipoprotein profile, and an imbalance in cholesterol homeostasis. Since periodontopathogenic potential differs between serotypes of a major periodontal pathogen, Actinobacillus actinomycetemcomitans, we studied the pro-atherogenic properties of LPS preparations from serotypes b and d strains on macrophages (RAW 264.7). A. actinomycetemcomitans LPS preparations induced a time-dependent release of tumor necrosis factor- (TNF-) and interleukin-1ß (IL-1ß). LPS induced foam cell formation and cholesteryl ester accumulation from native low density lipoprotein in the following order: A. actinomycetemcomitans strains JP2 (serotype b) > Y4 (serotype b) > IDH781 (serotype d). mRNA expression levels of scavenger receptor class B, type-I, and ATP-binding cassette transporter-1, receptors mediating cholesterol efflux from macrophages, were decreased by LPS preparations. The results suggest that the pro-atherogenic potential of A. actinomycetemcomitans LPS may depend on the infecting strain and correlate with the periodontopathogenic potential of the pathogen.

Key Words: Foam cell formation • infection • inflammation • periodontitis • RAW 264.7 macrophages • SR-BI • ABCA-1

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