Year: 2012
Type: dissertation
Abstract: Mast cells are immunological cells having an important function in host defense. Mast cells also participate in the regulation of many other physiological functions of the body, such as the regulation of tissue homeostasis, intestinal functions, and neuro-immune interactions, by producing multiple mediators including cytokines, chemokines, leukotrienes, prostaglandins, proteases, and biogenic amines. However, these same mast cell-derived mediators are involved in the pathogenesis of many inflammatory diseases, such as atherosclerosis and other metabolic disorders, as well as allergy and intestinal diseases. Considering the inflammatory nature of atherosclerosis, exploring the role of infection in the pathogenesis of the disease has recently gained attention. Components of microbial origin have been detected in atherosclerotic lesions and are suggested to promote the inflammatory status in the arteries. On the other hand, microbes with beneficial effects on human health, called probiotics, have been under extensive study regarding their ability to modulate immunological functions and, thus, their possible benefits in the prevention and alleviation of inflammatory diseases. The purpose of the present study was to investigate the ability of atherosclerosis-related and probiotic bacteria to activate mast cells and their possible effects on inflammation caused by infection or diet. The proatherogenic bacteria Chlamydia pneumoniae (Cpn) and Aggregatibacter actinomycetemcomitans (Aa) induced pro-inflammatory effects in cultured human peripheral-derived mast cells characterized by the elevated expression and secretion of pro-inflammatory cytokines, including tumor necrosis factor α (TNF-α), and chemokines, such as interleukin (IL)-8 and chemokine (C-C motif) ligand 2 (CCL-2). Cpn and Aa also increased the number of activated mast cells in the aortas of atherosclerosis-prone ApoE-/- mice. Aa was also observed to induce increased concentrations of serum lipopolysaccharide (LPS) and TNF-α in the mice. The probiotic Lactobacillus rhamnosus GG (GG) and Lactobacillus rhamnosus Lc705 (Lc705) induced the downregulation of several mast cell activation-related genes in cultured human peripheral-derived mast cells. In addition, GG, Lc705, Bifidobacterium animalis ssp. lactis Bb12 (Bb12), and a combination of these three strains with Propionibacter freudenreichii ssp. shermanii JS (PJS) upregulated the expression of Th1 type pro-inflammatory cytokines, including TNF-α and IL-1β, and chemokines CCL-2 and IL-8, as well as the anti-inflammatory cytokine IL-10. The administration of GG and PJS to high fat-fed ApoE*3Leiden mice reduced the number of intestinal mast cells and the concentrations of plasma markers of inflammation, including vascular cell adhesion molecule (VCAM) 1 E-selectin, and serum amyloid A (SAA). In conclusion, Cpn and Aa induced pro-inflammatory actions in cultured mast cells as well as the activation of mast cells and the induction of systemic inflammation markers in vivo. These effects might induce the inflammation in atherosclerotic lesions and, thus, promote the development of atherosclerosis. The probiotic GG and Lc705 suppressed the expression of genes related to mast cell activation and induced the production of Th1 type and anti-inflammatory cytokines. These changes are suggested to alleviate allergic inflammation. In addition, GG and PJS elicited several anti-inflammatory effects in mice with high-fat diet-induced inflammation, including decreases in the numbers of intestinal mast cells and in the concentrations of markers of systemic inflammation. These actions could be beneficial in the prevention or treatment of inflammatory diseases, such as metabolic disorders.
Source: Työväentutkimus Vuosikirja
Author: Anna Oksaharju
Language: English
Topic: Mast cells and histamine
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
Funder: Valio
OpenAlex ID: W2130130684