Bactericidal/permeability‐increasing protein inhibits endotoxin‐induced vascular nitric oxide synthesis

Ciornei, Cristina; Egesten, Arne; Engström, Martin; Törnebrandt, K.; Bodelsson, Mikael

doi:10.1034/j.1399-6576.2002.460909.x

Cited by 21 publications

(12 citation statements)

References 35 publications

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“…As expected, LPS and IL-1b increased the production of nitrate/ nitrite in the vessel segments (25). LL-37 reduced the LPS-induced nitrate/nitrite production, which confirms that LL-37 can inhibit the LPS-induced NO production in rat aorta.…”

Section: Discussionsupporting

confidence: 83%

Effects of human cathelicidin antimicrobial peptide LL‐37 on lipopolysaccharide‐induced nitric oxide release from rat aorta in vitro

Ciornei

Egesten

Bodelsson

2003

Acta Anaesthesiol Scand

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Background: Lipopolysaccharides (LPS), released by Gram‐negative bacteria, cause vascular expression of inducible nitric oxide synthase (iNOS) leading to nitric oxide (NO) production and septic shock. Human cathelicidin antimicrobial peptide (LL‐37) can bind and neutralize LPS. We wanted to study whether LL‐37 affects LPS or interleukin‐1β (IL‐1β)‐induced production, release and function of NO in intact rat aorta rings and cultured rat aorta smooth muscle cells.Methods: Isolated segments of thoracic aorta and cultured cells were incubated in the presence of LPS, LL‐37, LPS + IL‐37, IL‐1β, IL‐1β + IL‐37 or in medium alone. Smooth muscle contraction in response to phenylephrine and accumulation of the sdegradation products of NO, nitrate and nitrite, were measured on aorta segments. Levels of iNOS were assessed by Western blot and cytotoxic effects were detected by measurement of DNA fragmentation in cultured cells. Number of viable cells were determined after Trypan blue treatment.Results: Both LPS and IL‐1β reduced contractility in response to phenylephrine and increased NO production as well as iNOS expression. LL‐37 inhibited the LPS depression of vascular contractility induced only by LPS. LL‐37 reduced both the LPS‐ and IL‐1β‐induced NO production and iNOS expression. LL‐37 at high concentrations induced DNA fragmentation and decreased the number of living cells.Conclusion: IL‐37 reduces NO production induced by LPS and IL‐1β. The reduction does not seem to result only from neutralization of LPS but also from a cytotoxic effect, possibly via induction of apoptosis.

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Section: Discussionsupporting

confidence: 83%

Effects of human cathelicidin antimicrobial peptide LL‐37 on lipopolysaccharide‐induced nitric oxide release from rat aorta in vitro

Ciornei

Egesten

Bodelsson

2003

Acta Anaesthesiol Scand

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“…A two-tailed t test was performed, and the results significant at a P value of Ͻ0.05 are marked with an asterisk, and those significant at a P value of Ͻ0.001 are marked by a double asterisk. tion that is a hallmark of sepsis has led to their consideration as antisepsis agents (3,13,17). However, toxicity due to the relatively high concentrations of peptide required is a major concern.…”

Section: Discussionmentioning

confidence: 99%

Immunomodulatory Activities of Small Host Defense Peptides

Bowdish

Davidson

Scott

et al. 2005

Antimicrob Agents Chemother

293

213

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Recent studies have demonstrated that in addition to their antimicrobial activity, cationic host defense peptides, like the human cathelicidin LL-37, perform many activities relating to innate immunity, including the induction or modulation of chemokine and cytokine production, alteration of gene expression in host cells, and inhibition of proinflammatory responses of host cells to bacterial components such as lipopolysaccharide (LPS) in vitro and in vivo. To investigate if these properties are shared by smaller peptides, two cathelicidin peptides derived from bovine neutrophils, the 13-mer indolicidin and Bac2A, a linear 12-amino-acid derivative of bactenecin, were compared to the 37-amino-acid peptide LL-37. Indolicidin, like LL-37, inhibited LPSinduced tumor necrosis factor alpha (TNF-␣) secretion, even when added up to an hour after the addition of Escherichia coli O111:B4 LPS to the human macrophage/monocyte-like THP-1 cell line. In contrast, Bac2A demonstrated no significant antiendotoxin activity. At low concentrations, indolicidin and LL-37 acted synergistically to suppress LPS-induced production of TNF-␣. Indolicidin was analogous to LL-37 in its ability to induce the production of the chemokine interleukin-8 (IL-8) in a human bronchial cell line, 16HBE14o؊ , but it was unable to induce production of IL-8 in THP-1 cells. In contrast, Bac2A was unable to induce IL-8 in either cell type. Conversely, Bac2A was chemotactic for THP-1 cells at concentrations between 10 and 100 g/ml, while indolicidin and LL-37 were not chemotactic at these concentrations for THP-1 cells. This indicates that in addition to the potential for direct microbicidal activity, cationic host defense peptides may have diverse and complementary abilities to modulate the innate immune response.

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“…As BPI binds the lipid A region common to all LPS, it is able to neutralize endotoxin from a broad array of Gram-negative pathogens [9,37]. Thus, BPI is capable of inhibiting the proinflammatory activities of LPS, including induction of cytokine release, activation of the neutrophil oxidase enzyme and NO formation [36][37][38][39]. The opsonic activity of BPI occurs via binding of the Nterminal domain to Gram-negative bacteria and promotion, via the C-terminal portion of BPI, of bacterial attachment to neutrophils and monocytes [19].…”

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confidence: 99%

Bactericidal/permeability-increasing protein (BPI) and BPI homologs at mucosal sites

Canny

Levy

2008

Trends in Immunology

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Bactericidal/permeability‐increasing protein inhibits endotoxin‐induced vascular nitric oxide synthesis

Cited by 21 publications

References 35 publications

Effects of human cathelicidin antimicrobial peptide LL‐37 on lipopolysaccharide‐induced nitric oxide release from rat aorta in vitro

Effects of human cathelicidin antimicrobial peptide LL‐37 on lipopolysaccharide‐induced nitric oxide release from rat aorta in vitro

Immunomodulatory Activities of Small Host Defense Peptides

Bactericidal/permeability-increasing protein (BPI) and BPI homologs at mucosal sites

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