Differential Expression of IL-1β, TNF-α, IL-6, and IL-8 in Human Monocytes in Response to Lipopolysaccharides from Different Microbes

Abstract

Macrophages respond to bacterial lipopolysaccharides (LPS) and activate several host defense functions through production of mediators. However, it is not clear whether the degree of macrophage responsiveness to different sources of LPS is equivalent to or varies with the source of LPS. Therefore, in this report, we examined the extent of the human monocyte response to LPS derived from two oral pathogens, Actinobacillus actinomycetemcomitans (Aa) and Porphyromonas gingivalis (Pg). Additionally, due to its well-established ability to activate monocytes, we used LPS from Escherichia coli (Ec). Human monocytes, when activated with a specific source of LPS, exhibited rapid expression of mRNA for IL-1 beta, TNF-alpha, and IL-8, which was followed by IL-6, as measured by RNA-PCR. Moreover, the expression of mRNA for these cytokines was followed by cytokine synthesis. Monocytes from the same subject, when activated with LPS from Pg, Aa, or Ec expressed quantitatively different levels of mRNA and proteins for all four cytokines. A given LPS induced either high or low expression of the battery of cytokines tested, indicating that the expression of these pro-inflammatory cytokines may be regulated by a single or a cluster of gene(s). However, no apparent differences in the time course of mRNA expression for these cytokines were observed in response to any of the LPS tested. Furthermore, the relative ability of the different sources of LPS to induce mRNA for cytokines varied throughout a wide range of LPS concentrations. This suggests that differences exist in the sensitivity of monocytes to a specific LPS, rather than in the kinetics of the secretory process itself.(ABSTRACT TRUNCATED AT 250 WORDS)

Interaction of lactic acid bacteria with the gut immune system

“…Initially, the immunomodulating capacity of LAB was only referred to the induction of antibody production or the cellular response. Actually, considering the important role played by biological messengers as cytokines in the balance of the immune response, a lot of research work has been done to demonstrate the influence of LAB in the cytokine release signalling pathways for the production of cytokines (Agarwal et al, 1995;Miettinen et al, 1996Miettinen et al, , 2000Maassen et al, 2000).…”

Polymorphonuclear leucocyte (PMN)-derived inflammatory cytokines—regulation by oxygen tension and extracellular matrix

“…Recently, the neutrophil has been shown to have the ability to produce a number of immunomodulators, cytokines in particular, that may regulate the inflammatory cascade [3][4][5][6]. Among those, IL-8, TNF-and IL-1 have particular importance [3,[7][8][9][19][20][21]. At sites of inflammation, as well as in the systemic circulation, leucocytes elaborate cytokines in response to various proinflammatory agonists.…”

“…IL-8, TNF-and IL-1 have been shown to strongly influence neutrophil function in a variety of experimental and clinical settings [3,[7][8][9]. Further, PMN function is regulated by its interactions with extracellular matrix through integrin molecules [2,[10][11][12].…”

The role of macrophages in the induction of murine immune response to Actinobacillus actinomycetemcomitans

“…Evidence has shown that the numbers of this micro-organism are increased in patients with periodontal disease, especially those with early-onset periodontitis [3][4][5][6]. Human monocytes and polymorphonuclear neutrophils stimulated with this potential periodontopathogen have been shown to release proinflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-8 and tumour necrosis factor (TNF-AE) [7,8]. A. actinomycetemcomitans has been shown to induce alveolar bone destruction in animal models [9].…”