Resistance to lipopolysaccharide mediated by the Yersinia pestis V antigen-polyhistidine fusion peptide: Amplification of interleukin-10

Yuri A. Nedialkov, Vladimir Motin, Robert R. Brubaker

Research output: Contribution to journalArticle

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Abstract

We previously showed that injection of homogenous staphylococcal protein A-V antigen fusion peptide into mice delayed allograft rejection and suppressed the major proinflammatory cytokines tumor necrosis factor alpha (TNF-α) and gamma interferon (IFN-γ) associated with generation of protective granulomas. This study was undertaken to determine if V antigen could prevent endotoxic shock, known to be mediated by excessive production of certain proinflammatory cytokines. After treatment with 50 μg of homogeneous V antigen-polyhistidine fusion peptide (V(h)), the 50% lethal dose of purified lipopolysaccharide (LPS) in BALB/c mice immediately rose from 63 μg (normal controls) to 318 μg, fell to near baseline (71 μg) in 6 h, and then slowly rose to a maximum of 566 μg at 48 h before again returning to normal. Injected V(h) alone (50 μg) promptly induced the anti- inflammatory cytokine interleukin-10 (IL-10) as well as modest levels of TNF- α (an inducer of IL-10) in spleen. Concomitant injection of V(h) and an otherwise lethal dose of LPS (200 μg) dramatically decreased levels of TNF- α and IFN-γ in the spleen and peritoneal lavage fluid as compared to values determined for LPS alone. These results would be expected if V antigen directly up-regulated IL-10 that is reported to generally down-regulate proinflammatory cytokines. Mice receiving 200 μg of LPS 48 h after injection of V(h) exhibited patterns of cytokine synthesis similar to those observed in endotoxin-tolerant mice, a condition also reported to be mediated by IL-10. These findings suggest that V antigen serves as a virulence factor by amplifying IL-10, thereby repressing proinflammatory cytokines required for expression of cell-mediated immunity.

Original languageEnglish (US)
Pages (from-to)1196-1203
Number of pages8
JournalInfection and Immunity
Volume65
Issue number4
StatePublished - 1997
Externally publishedYes

Fingerprint

Yersinia pestis
Interleukin-10
Lipopolysaccharides
Cytokines
Antigens
Peptides
Tumor Necrosis Factor-alpha
Injections
Spleen
Peritoneal Lavage
Ascitic Fluid
Lethal Dose 50
Staphylococcal Protein A
Virulence Factors
Septic Shock
Granuloma
Interferon-alpha
Endotoxins
Cellular Immunity
Interferon-gamma

ASJC Scopus subject areas

  • Immunology

Cite this

Resistance to lipopolysaccharide mediated by the Yersinia pestis V antigen-polyhistidine fusion peptide : Amplification of interleukin-10. / Nedialkov, Yuri A.; Motin, Vladimir; Brubaker, Robert R.

In: Infection and Immunity, Vol. 65, No. 4, 1997, p. 1196-1203.

Research output: Contribution to journalArticle

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