Differential cytokine response in host defence mechanisms triggered by gram-negative and gram-positive bacteria, and the roles of gabexate mesilate, a synthetic protease inhibitor.
Bacterial infection results in the production of inflammatory mediators and may be involved in the pathogenesis of sepsis and/or systemic inflammatory response syndrome. The effect of lipopolysaccharide (LPS), a major component of the outer surface of Gram-negative bacteria, and Staphylococcal enterotoxin B (SEB), a superantigen of Gram-positive bacteria, on cytokine production in peripheral blood mononuclear cells (PBMCs) was examined. LPS significantly increased the production of proinflammatory and anti-inflammatory cytokines, and SEB enhanced the production of helper T lymphocyte type cytokines. These results illustrated the different responses to Gram-negative and Gram-positive bacterial infections. The effect of gabexate mesilate, a synthetic protease inhibitor, on cytokine production and expression of the toll-like receptor (TLR) was also examined. The results suggest that gabexate mesilate-induced inhibition of tumour necrosis factor-alpha (TNF-alpha) and interleukin-18 (IL-18) production in LPS-stimulated PBMCs is due to the inhibition of the nuclear factor-kappa B activation pathway and/or inhibition of the processing pathway of pro-TNF-alpha and pro-IL-18, not to down-regulation of TLR-2 or TLR-4.
Iwadou
H
H
First Department of Surgery, Okayama University Medical School, Okayama, Japan.
Morimoto
Y
Y
Iwagaki
H
H
Sinoura
S
S
Chouda
Y
Y
Kodama
M
M
Yoshioka
T
T
Saito
S
S
Yagi
T
T
Tanaka
N
N
D015703:Antigens, CD / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D029721:Drosophila Proteins; D004768:Enterotoxins / Q000276:immunology / Q000494:pharmacology*; D016670:Gabexate / Q000494:pharmacology* / Q000627:therapeutic use; D006090:Gram-Negative Bacteria / Q000276:immunology / Q000378:metabolism; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000276:immunology; D006094:Gram-Positive Bacteria / Q000276:immunology / Q000378:metabolism; D016908:Gram-Positive Bacterial Infections / Q000188:drug therapy / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D020382:Interleukin-18 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018124:Receptors, Tumor Necrosis Factor / Q000276:immunology / Q000378:metabolism; D047889:Receptors, Tumor Necrosis Factor, Type II; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D012795:Sialoglycoproteins / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D018089:Superantigens / Q000276:immunology / Q000494:pharmacology; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism*
D015703:Antigens, CD; D029721:Drosophila Proteins; D004768:Enterotoxins; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D020382:Interleukin-18; D007376:Interleukin-2; D015850:Interleukin-6; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011956:Receptors, Cell Surface; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D015842:Serine Proteinase Inhibitors; D012795:Sialoglycoproteins; D018089:Superantigens; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal; D016670:Gabexate; D007371:Interferon-gamma