CD14-dependent and -independent cytokine and chemokine production by human THP-1 monocytes stimulated byStreptococcus suiscapsular type 2

Segura, Mariela; Vadeboncoeur, Nathalie; Gottschalk, Marcelo

doi:10.1046/j.1365-2249.2002.01768.x

Cited by 80 publications

(107 citation statements)

References 47 publications

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“…Segura et al showed that the release of TNFα, IL1, IL6, and MCP1 was increased after 48 hours' stimulation with 1 μg/mL LPS, the concentration for each mediator being higher than the level shown in the present study, but this difference could be explained by the difference in the concentration of LPS used for cell activation (1 μg/mL compared with 100 ng/mL in our experiments). 33 Our study demonstrates that Lipo/GOT completely blocked the secretion of IL1β, IL6, TNFα, and MCP1 compared with free GOT, which did not decrease the secretion of these cytokines/chemokines induced by LPS. This effect of Lipo/GOT vs free GOT may be explained by increased cellular internalization of the compound when it is formulated into Lipo and gradual intracellular release, whereas the free compound acts very rapidly or is committed to intracellular degradation.…”

Section: Discussionmentioning

confidence: 51%

Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor

Pirvulescu¹,

Rebleanu²,

Constantinescu³

et al. 2017

IJN

105

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Background Lipopolysaccharide (LPS) is widely recognized as a potent activator of monocytes/macrophages, and its effects include an altered production of key mediators, such as inflammatory cytokines and chemokines. The involvement of G i protein in mediating LPS effects has been demonstrated in murine macrophages and various cell types of human origin. Purpose The aim of the present work was to evaluate the potential of a G i -protein inhibitor encapsulated in liposomes in reducing the inflammatory effects induced by LPS in monocytes/macrophages. Materials and methods Guanosine 5′- O -(2-thiodiphosphate) (GOT), a guanosine diphosphate analog that completely inhibits G-protein activation by guanosine triphosphate and its analogs, was encapsulated into liposomes and tested for anti-inflammatory effects in LPS-activated THP1 monocytes or THP1-derived macrophages. The viability of monocytes/macrophages after incubation with different concentrations of free GOT or liposome-encapsulated GOT was assessed by MTT assay. MAPK activation and production of IL1β, TNFα, IL6, and MCP1 were assessed in LPS-activated monocytes/macrophages in the presence or absence of free or encapsulated GOT. In addition, the effect of free or liposome-encapsulated GOT on LPS-stimulated monocyte adhesion to activated endothelium and on monocyte chemotaxis was evaluated. Results We report here that GOT-loaded liposomes inhibited activation of MAPK and blocked the production of the cytokines IL1β, TNFα, IL6, and MCP1 induced by LPS in monocytes and macrophages. Moreover, GOT encapsulated in liposomes reduced monocyte adhesion and chemotaxis. All demonstrated events were in contrast with free GOT, which showed reduced or no effect on monocyte/macrophage activation with LPS. Conclusion This study demonstrates the potential of liposomal GOT in blocking LPS proinflammatory effects in monocytes/macrophages.

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Section: Discussionmentioning

confidence: 51%

Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of Gi-protein inhibitor

Pirvulescu¹,

Rebleanu²,

Constantinescu³

et al. 2017

IJN

105

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“…It is reasonable to explain this phenomenon by the thicker capsule of the ⌬covR strain, since it has been reported that the capsular polysaccharide (CPS) of S. suis protects against phagocytosis and against the bactericidal activity of leukocytes (6,9,48,59,62,63,79). The work of Segura et al demonstrated that S. suis serotype 2 is able to interact with MONOs of human origin, inducing the release of large amounts of the proinflammatory cytokines (61).…”

Section: Discussionmentioning

confidence: 99%

The Orphan Response Regulator CovR: a Globally Negative Modulator of Virulence inStreptococcus suisSerotype 2

Pan

et al. 2009

J Bacteriol

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Streptococcus suis serotype 2 is an emerging zoonotic pathogen responsible for a wide range of life-threatening diseases in pigs and humans. However, the pathogenesis of S. suis serotype 2 infection is not well understood. In this study, we report that an orphan response regulator, CovR, globally regulates gene expression and negatively controls the virulence of S. suis 05ZYH33, a streptococcal toxic shock syndrome (STSS)-causing strain. A covR-defective (⌬covR) mutant of 05ZYH33 displayed dramatic phenotypic changes, such as formation of longer chains, production of thicker capsules, and increased hemolytic activity. Adherence of the ⌬covR mutant to epithelial cells was greatly increased, and its resistance to phagocytosis and killing by neutrophils and monocytes was also significantly enhanced. More importantly, inactivation of covR increased the lethality of S. suis serotype 2 in experimental infection of piglets, and this phenotype was restored by covR complementation. Colonization experiments also showed that the ⌬covR mutant exhibited an increased ability to colonize susceptible tissues of piglets. The pleiotropic phenotype of the ⌬covR mutant is in full agreement with the large number of genes controlled by CovR as revealed by transcription profile analysis: 2 genes are positively regulated, and 193 are repressed, including many that encode known or putative virulence factors. These findings suggested that CovR is a global repressor in virulence regulation of STSS-causing S. suis serotype 2.

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“…First, encapsulated S. suis is able to adhere to the surface of phagocytes, and the CPS itself is involved in such adhesion (41). Second, encapsulated S. suis is able to induce the release of proinflammatory cytokines by phagocytes by an adhesion-dependent process (42,43). However, the levels of induced cytokines are lower than those induced by the nonencapsulated mutant (42,48).…”

Section: Discussionmentioning

confidence: 99%

EncapsulatedStreptococcus suisInhibits Activation of Signaling Pathways Involved in Phagocytosis

2004

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Streptococcus suis capsular type 2 is an important zoonotic agent of meningitis. Previous studies reported that, in contrast to nonencapsulated mutants, encapsulated S. suis is able to resist phagocytosis. However, the mechanisms by which S. suis avoids phagocytosis are unknown. To elucidate the signaling pathway(s) involved in S. suis antiphagocytosis, we compared the ability of an encapsulated strain and its nonencapsulated mutant to induce the activation of Akt and protein kinase C (PKC), which are downstream kinases of the phosphatidylinositol 3-kinase (PI-3K) pathway, known to be involved in the phagocytosis processes. The results demonstrated high levels of Akt and PKC␣ phosphorylation after infection of J774 macrophages with the nonencapsulated mutant, whereas the encapsulated strain showed reduced activation of PI-3K/Akt/PKC␣ signaling pathway, as well as several protein tyrosine events. These results correlated with the number of intracellular bacteria. Macrophages pretreated with specific PI-3K or PKC inhibitors showed reduced levels of Akt and PKC␣ phosphorylation, resulting in 50% reduction of phagocytosis. The role of phosphatases in the antiphagocytic mechanisms was evaluated by using phosphatase inhibitors, as well as SHP-1-deficient macrophages. Only in the absence of SHP-1 did the phagocytosis of encapsulated S. suis significantly increase, leading to Akt phosphorylation levels similar to those observed with the nonencapsulated strain, indicating activation of this important SH2 domain-containing tyrosine phosphatase by encapsulated S. suis. Finally, when purified S. suis capsular polysaccharide (CPS) was added to macrophages, no phosphorylation events were observed. In addition, CPS and encapsulated S. suis were able to inhibit the uptake of the nonencapsulated mutant. These results suggest the importance of CPS in the mechanisms, whereby S. suis downmodulates phagocytosis.

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CD14-dependent and -independent cytokine and chemokine production by human THP-1 monocytes stimulated byStreptococcus suiscapsular type 2

Cited by 80 publications

References 47 publications

Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G<sub>i</sub>-protein inhibitor

Lipopolysaccharide-induced inflammation in monocytes/macrophages is blocked by liposomal delivery of G<sub>i</sub>-protein inhibitor

The Orphan Response Regulator CovR: a Globally Negative Modulator of Virulence inStreptococcus suisSerotype 2

EncapsulatedStreptococcus suisInhibits Activation of Signaling Pathways Involved in Phagocytosis

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