Induction of CC chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline

Krakauer, Teresa

doi:10.1002/jlb.66.1.158

Cited by 56 publications

(69 citation statements)

References 42 publications

(56 reference statements)

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“…The early response (4 -13 h) was associated with MCP-1 release and followed by secretion of IL-8 (13-48 h) and a later increase in IL-6 levels (24 -72 h). Induction of CXC and CC chemokines, including IL-8 and MCP-1, in human peripheral blood monocytes and fibroblast-like synoviocytes by staphylococcal superantigens has been reported (16,45). Moreover, the role of IL-8 as a key mediator of neutrophil transmigration to the SEA-induced mucosal inflammatory site has been established in staphylococcal enterotoxin-associated airway diseases (13,15).…”

Section: Discussionmentioning

confidence: 98%

Monocyte Chemoattractant Protein-1 Production by Intestinal Myofibroblasts in Response to Staphylococcal Enterotoxin A: Relevance to Staphylococcal Enterotoxigenic Disease

Pinchuk¹,

Beswick²,

Saada³

et al. 2007

The Journal of Immunology

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Food poisoning due to staphylococcal enterotoxins A and B (SEA and SEB) affects hundreds of thousands of people annually. SEA and SEB induce massive intestinal cytokine production, which is believed to be the key factor in staphylococcal enterotoxin enteropathy. MHC class II molecules are the major receptors for staphylococcal enterotoxins. We recently demonstrated that normal human subepithelial intestinal myofibroblasts (IMFs) express MHC class II molecules. We hypothesized that IMFs are among the first cells to respond to staphylococcal enterotoxins and contribute to the cytokine production associated with staphylococcal enterotoxin pathogenesis. We demonstrated here that primary cultured IMFs bind staphylococcal enterotoxins in a MHC class II-dependent fashion in vitro. We also demonstrated that staphylococcal enterotoxins can cross a CaCo-2 epithelial monolayer in coculture with IMFs and bind to the MHC class II on IMFs. IMFs responded to SEA, but not SEB, exposure with 3- to 20-fold increases in the production of proinflammatory chemokines (MCP-1, IL-8), cytokines (IL-6), and growth factors (GM-CSF and G-CSF). The SEA induction of the proinflammatory mediators by IMFs resulted from the efficient cross-linking of MHC class II molecules because cross-linking of class II MHC by biotinylated anti-HLA-DR Abs induced similar cytokine patterns. The studies presented here show that MCP-1 is central to the production of other cytokines elicited by SEA in IMFs because its neutralization with specific Abs prevented the expression of IL-6 and IL-8 by IMFs. Thus, MCP-1 may play a leading role in initiation of inflammatory injury associated with staphylococcal enterotoxigenic disease.

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Section: Discussionmentioning

confidence: 98%

Monocyte Chemoattractant Protein-1 Production by Intestinal Myofibroblasts in Response to Staphylococcal Enterotoxin A: Relevance to Staphylococcal Enterotoxigenic Disease

Pinchuk¹,

Beswick²,

Saada³

et al. 2007

The Journal of Immunology

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“…SEB and other related toxins produced by S. aureus and Streptococcus pyogenes (i.e., toxic shock syndrome toxin 1 [TSST-1] plus the pyrogenic exotoxins) possess superantigenic properties that entail a marked activation of T lymphocytes with subsequent release of proinflammatory cytokines and chemokines (12)(13)(14)(15)(16). In large quantities, these molecules can play an important role in ill effects experienced by the host following exposure to SEB or other related protein superantigens.…”

mentioning

confidence: 99%

“…In contrast to Vibrio cholerae cholera toxin, which activates host adenylate cyclase, intracellular amounts of cAMP elicited by B. anthracis edema toxin rise more rapidly to even higher levels with a minimal lag period (17,18). Finally, in contrast to edema toxin, T-lymphocyte proliferation with subsequently elevated levels of proinflammatory cytokines/ chemokines represents a classic effect caused by superantigen stimulation of the immune system (12)(13)(14)(15)(16). The results from the present study reveal a novel means of inhibiting SEB activity in vitro by using B. anthracis edema toxin.…”

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confidence: 99%

Bacillus anthracisEdema Toxin InhibitsStaphylococcus aureusEnterotoxin B Effects In Vitro: a Potential Protein Therapeutic?

Krakauer¹,

Little

Stiles³

2005

Infect Immun

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Various in vitro effects of staphylococcal enterotoxin B (SEB) on human peripheral blood mononuclear cells were mitigated by Bacillus anthracis edema toxin. In particular, levels of some SEB-induced cytokines (tumor necrosis factor alpha, gamma interferon) and chemokines (monocyte chemoattractant protein 1, macrophage inflammatory protein 1 alpha [MIP-1␣], MIP-1␤) were significantly diminished or even nonexistent, depending upon the timing of edema toxin administration. Overall, these results suggest a novel use of B. anthracis edema toxin against a bacterial superantigen.Bacillus anthracis and Staphylococcus aureus are gram-positive pathogens involved in numerous human/animal diseases that include skin-linked maladies such as cutaneous anthrax, carbuncles, impetigo, and scalded-skin syndrome (16,35). The various protein toxins produced by these bacteria (i.e., B. anthracis lethal toxin or S. aureus enterotoxins/toxic shock syndrome toxin 1) can profoundly affect a host in multiple ways, which may result in morbidity, shock, and even death. Furthermore, B. anthracis and staphylococcal enterotoxin B (SEB) are considered by the Centers for Disease Control and Prevention to be select agents that warrant monitoring by the federal government. Therefore, a renewed interest in B. anthracis and SEB as bioterror threats has caused some academic, government, and industrial institutions to further investigate (or in some cases, stop investigating) the respective "biology" of this microorganism and toxin, with an immediate focus upon generating vaccines and therapeutics. Additionally, the continuing rise in antibiotic resistance among diverse clinical isolates throughout the world (e.g., vancomycin-resistant S. aureus) demands further attention now by researchers and clinicians, ultimately necessitating "novel" means of controlling bacterial pathogens and their toxins (22).SEB and other related toxins produced by S. aureus and Streptococcus pyogenes (i.e., toxic shock syndrome toxin 1 [TSST-1] plus the pyrogenic exotoxins) possess superantigenic properties that entail a marked activation of T lymphocytes with subsequent release of proinflammatory cytokines and chemokines (12-16). In large quantities, these molecules can play an important role in ill effects experienced by the host following exposure to SEB or other related protein superantigens. In vitro and in vivo studies by various groups have also shown that the adverse effects of the SEs and TSST-1 are naturally potentiated by a ubiquitous component of all gram-negative bacteria, namely, lipopolysaccharide (LPS) (4, 6, 30-32). It is this fact that suggests that an agent which blocks LPS effects might also abrogate SEB activity, as both commonly evoke elevated levels of proinflammatory cytokines and chemokines (8,(14)(15)(16).A previous study by Hoover et al. (9) reveals that B. anthracis edema factor (EF), a calcium/calmodulin-dependent adenylate cyclase that enters various eucaryotic cells via B. anthracis protective antigen (PA) (17-19), substantially decreases the p...

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“…With LPS-activated cells, IL-1␤, TNF-␣, IL-6, MCP-1, MIP-1␣, and MIP-1␤ production were blocked 33, 78, 41, 99, 61, and 59%, respectively, by D609. The inhibition of SEB-, TSST-, or LPS-induced chemokines by D609 is probably direct, since previous reports indicated that both SEB and LPS can stimulate PBMC to release these chemokines directly (13,22).…”

Section: Filters and Incorporated [mentioning

confidence: 90%

“…PBMC (10 6 cells/ml) were cultured at 37°C in 24-well plates containing RPMI 1640 medium and 10% heat-inactivated fetal bovine serum. Cells were incubated with either SEB (150 ng/ml), TSST-1 (150 ng/ml), or LPS (100 ng/ml) for 16 h, and the supernatants were harvested and analyzed for IL-1␤, Cytokines and chemokines were measured by an enzyme-linked immunosorbent assay (ELISA) with cytokine-or chemokine-specific antibodies according to the manufacturer's instructions (11,13). Human recombinant cytokines and chemokines (20 to 1,000 pg/ml) were used as standards for calibration on each plate.…”

mentioning

confidence: 99%

Suppression of Endotoxin- and Staphylococcal Exotoxin-Induced Cytokines and Chemokines by a Phospholipase C Inhibitor in Human Peripheral Blood Mononuclear Cells

Krakauer

2001

Clin Diagn Lab Immunol

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Excessive release of proinflammatory cytokines from cells stimulated with lipopolysaccharide (LPS) or staphylococcal exotoxin (SE) mediates the pathophysiologic manifestations of septic shock. Tricyclodecan-9-yl (D609), an inhibitor of phosphatidylcholine-specific phospholipase C, suppressed LPS-or SE-induced cytokines and chemokines in human peripheral blood mononuclear cells. These data suggest a potential role for D609 in the treatment of septic shock.Lipopolysaccharide (LPS) and staphylococcal exotoxins (SE) are among the most common etiological agents causing septic shock (2,10,18). Although these bacterial products interact with host cells through different receptors, they trigger excessive systemic release of inflammatory cytokines, resulting in septic shock. LPS from gram-negative bacteria binds to serum LPS-binding protein, which then facilitates its binding to the cell surface protein CD14 on monocytes/macrophages and other cells (21). The subsequent interaction of LPS-CD14 complex with Toll-like receptors on these cells initiates transmembrane signaling and cellular activation to secrete cytokines and chemokines (15).Staphylococcal toxic shock syndrome toxin 1 (TSST-1), and the structurally related enterotoxins, are bacterial exotoxins that bind directly to major histocompatibility complex class II molecules on antigen-presenting cells (APC) (4,8,19) and stimulate T cells expressing specific V␤ elements (5, 9). These toxins are called superantigens because of their ability to polyclonally activate large populations of T cells (10). Interaction of SE with APC and T cells also results in hyperproduction of cytokines and chemokines, which is responsible for the pathogenesis of toxic shock (16). These cytokines include tumor necrosis factor alpha (TNF-␣), gamma interferon (IFN-␥), and interleukin 1 (IL-1), proinflammatory mediators with potent immunoenhancing effects (12). In addition, levels of circulating TNF-␣ and IL-1 correlate with the clinical symptoms of sepsis or septic shock (3).In the last decade, numerous clinical trials conducted with antagonists to key mediators such as TNF-␣ (1, 7) or IL-1 (6) have not yielded significant therapeutic benefits for septic patients partly because sepsis is not the result of the release of any one cytokine. Thus, inhibitors that suppress multiple proinflammatory cytokines may be more efficacious for the treatment of septic shock. Recent studies show tricyclodecan-9-yl (D609), a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), protects mice from lethal shock induced either by TNF-␣, LPS, or staphylococcal enterotoxin B (SEB) (14). Surprisingly, D609 did not reduce the SEB-induced IL-1, TNF-␣, or IFN-␥ levels in these animals (14). The proposed mechanism of action of D609 is via blockade of the cytotoxic action of TNF-␣. In another study, D609 improved the survival of mice with LPS-induced shock (20), accompanied by a reduction in the levels of IL-1 and IL-6, but not TNF-␣, in serum. In the present study, the modulatory effect of D609 o...

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Induction of CC chemokines in human peripheral blood mononuclear cells by staphylococcal exotoxins and its prevention by pentoxifylline

Cited by 56 publications

References 42 publications

Monocyte Chemoattractant Protein-1 Production by Intestinal Myofibroblasts in Response to Staphylococcal Enterotoxin A: Relevance to Staphylococcal Enterotoxigenic Disease

Monocyte Chemoattractant Protein-1 Production by Intestinal Myofibroblasts in Response to Staphylococcal Enterotoxin A: Relevance to Staphylococcal Enterotoxigenic Disease

Bacillus anthracisEdema Toxin InhibitsStaphylococcus aureusEnterotoxin B Effects In Vitro: a Potential Protein Therapeutic?

Suppression of Endotoxin- and Staphylococcal Exotoxin-Induced Cytokines and Chemokines by a Phospholipase C Inhibitor in Human Peripheral Blood Mononuclear Cells

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