Open AccessPro‐atherogenic lung and oral pathogens induce an inflammatory response in human and mouse mast cells
Author(s) -
Oksaharju Anna,
Lappalainen Jani,
Tuomainen Anita M.,
Pussinen Pirkko J.,
Puolakkainen Mirja,
Kovanen Petri T.,
Lindstedt Ken A.
Publication year - 2009
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/j.1582-4934.2008.00285.x
Subject(s) - tumor necrosis factor alpha , lipopolysaccharide , interleukin 33 , immunology , biology , secretion , monocyte , inflammation , microbiology and biotechnology , mast cell , proinflammatory cytokine , connective tissue , interleukin , cytokine , endocrinology , genetics
A broad variety of microbes are present in atherosclerotic plaques and chronic bacterial infection increases the risk of atherosclerosis by mechanisms that have remained vague. One possible mechanism is that bacteria or bacterial products activate plaque mast cells that are known to participate in the pathogenesis of atherosclerosis. Here, we show by real‐time PCR analysis and ELISA that Chlamydia pneumoniae (Cpn) and a periodontal pathogen, Aggregatibacter actinomycetemcomitans (Aa), both induce a time and concentration‐dependent expression and secretion of interleukin 8 (IL‐8), tumour necrosis factor‐α (TNF‐α) and monocyte chemoattractant protein‐1 (MCP‐1) by cultured human peripheral blood‐derived mast cells, but not anti‐inflammatory molecules, such as IL‐10 or transforming growth factor β1 (TGF‐β1). The IL‐8 and MCP‐1 responses were immediate, whereas the onset of TNF‐α secretion was delayed. The Cpn‐mediated pro‐inflammatory effect was attenuated when the bacteria were inactivated by UV‐treatment. Human monocyte‐derived macrophages that were pre‐infected with Cpn also induced a significant pro‐inflammatory response in human mast cells, both in cocultures and when preconditioned media from Cpn‐infected macrophages were used. Intranasal and intravenous administration of live Cpn and Aa, respectively induced an accumulation of activated mast cells in the aortic sinus of apolipoprotein E‐deficient mice, however, with varying responses in the systemic levels of lipopolysaccharide (LPS) and TNF‐α. Pro‐atherogenic Cpn and Aa induce a pro‐inflammatory response in cultured human connective tissue‐type mast cells and activation of mouse aortic mast cells in vivo .