G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus-induced suppression of TNF production in macrophages

Kim, Sung O.; Sheikh, Haroon I.; Ha, Soon Duck; Martins, Andrew J.; Reid, Gregor

doi:10.1111/j.1462-5822.2006.00763.x

Cited by 123 publications

(111 citation statements)

References 78 publications

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“…54 While the mechanism governing G-CSF-mediated cytokine inhibition remains unclear, recent studies have suggested a role for STAT3. 58,59 Collectively, these data suggest an important role for G-CSF in the down-regulation of the local inflammatory response.…”

Section: Discussionmentioning

confidence: 81%

Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection

Gregory¹,

Hogue

Ferkol

et al. 2006

Blood

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Granulocyte colony-stimulating factor (G-CSF) regulates the production, maturation, and function of neutrophils. Its expression is often induced during infection, resulting in high concentrations of G-CSF in inflammatory exudates and in the blood, suggesting that it may regulate both local and systemic neutrophil responses. Herein, we characterize the neutrophil response in G-CSFR−/− mice following intratracheal injection with Pseudomonas aeruginosa–laden agarose beads, modeling the pulmonary infection observed in many patients with cystic fibrosis. G-CSFR−/− mice are markedly susceptible to bronchopulmonary P aeruginosa infection, exhibiting decreased survival and bacterial clearance as well as extensive damage to lung tissue. The systemic neutrophil response was mediated primarily by enhanced neutrophil release from the bone marrow rather than increased neutrophil production and was attenuated in G-CSFR−/− mice. Despite normal to increased local production of inflammatory chemokines, neutrophil accumulation into the infected lung of G-CSFR−/− mice was markedly reduced. Moreover, the percentage of apoptotic neutrophils in the lung was elevated, suggesting that G-CSF signals may play an important role in regulating neutrophil survival at the inflammatory site. Collectively, these data provide new evidence that G-CSF signals play important but specific roles in the regulation of the systemic and local neutrophil response following infection.

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Section: Discussionmentioning

confidence: 81%

Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection

Gregory¹,

Hogue

Ferkol

et al. 2006

Blood

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“…LR has been shown to be capable of inhibiting the onset of experimental colitis in transgenic IL-10-deficient mice (21) and has further been shown to reduce intestinal permeability to macromolecules (20). Probiotics are capable of inhibiting TNF production in activated macrophages (16,27). A recent publication by Lin et al (18) showed that LR suppressed the production of TNF from lipopolysaccharide-activated human monocytes/macrophages.…”

Section: Discussionmentioning

confidence: 99%

Protective effects of Lactobacillus reuteri and Bifidobacterium infantis in murine models for colitis do not involve the vagus nerve

Kleij¹,

O’Mahony²,

Shanahan³

et al. 2008

American Journal of Physiology-Regulatory, Integrative and Comp

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CD62Lϩ T lymphocytes from BALB/c into SCID mice. LR and BI (1 ϫ 10 9 ) were given daily. Clinical score, myeloperoxidase (MPO) levels, and in vivo and in vitro secreted inflammatory cytokine levels were found to be more severe in mice that were vagotomized compared with shamoperated animals. LR in the acute DSS model was effective in decreasing the MPO and cytokine levels in the tissue in sham and vagotomized mice. BI had a strong downregulatory effect on secreted in vitro cytokine levels and had a greater anti-inflammatory effect in vagotomized-compared with sham-operated mice. Both LR and BI retained anti-inflammatory effects in vagotomized mice. In SCID mice, vagotomy did not enhance inflammation, but BI was more effective in vagotomized mice than shams. Taken together, the intact vagus has a protective role in acute DSS-induced colitis in mice but not in the chronic T cell transfer model of colitis. Furthermore, LR and BI do not seem to engage their protective effects via this cholinergic anti-inflammatory pathway, but the results interestingly show that, in the T cell, transfer model vagotomy had a biological effect, since it increased the effectiveness of the BI in downregulation of colonic inflammation.

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“…Each blasticidin resistance clone was cultured for 2 wk and tested for TNF-␣ production in response to LPS (1 g/ml). TNF-␣ bioassay was performed as previously described (26). To rescue retroviral insertion-induced mutations, CTSB mut , a partial mRNA sequence of the fused gene product, was transfected with a retroviral vector expressing Cre (pBaBe-Cre) and puromycin resistance gene.…”

Section: Mutagenesis With Retrovirus Screening For Defects In Tnf-␣mentioning

confidence: 99%

Cathepsin B Is Involved in the Trafficking of TNF-α-Containing Vesicles to the Plasma Membrane in Macrophages

Martins

Khazaie

et al. 2008

The Journal of Immunology

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114

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TNF-α is a potent proinflammatory cytokine, essential for initiating innate immune responses against invading microbes and a key mediator involved in the pathogenesis of acute and chronic inflammatory diseases. To identify molecules involved in the production of TNF-α, we used a functional gene identification method using retroviral integration-mediated mutagenesis, followed by LPS-stimulated TNF-α production analysis in macrophages. We found that cathepsin B, a lysosomal cysteine proteinase, was required for optimal posttranslational processing of TNF-α in response to the bacterial cell wall component LPS. Mouse bone marrow-derived macrophages from cathepsin B-deficient mice and macrophages treated with the cathepsin B-specific chemical inhibitor CA074 methyl ester or small interfering RNA against cathepsin B secreted significantly less TNF-α than wild-type or nontreated macrophages. We further showed that the inhibition of cathepsin B caused accumulation of 26-kDa pro-TNF-containing vesicles. Ectopic expression of GFP-conjugated pro-TNF further suggests that pro-TNF failed to reach the plasma membrane without intracellular cathepsin B activity. Altogether, these data suggest that intracellular cathepsin B activity is involved in the TNF-α-containing vesicle trafficking to the plasma membrane.

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G-CSF-mediated inhibition of JNK is a key mechanism for Lactobacillus rhamnosus-induced suppression of TNF production in macrophages

Cited by 123 publications

References 78 publications

Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection

Regulation of systemic and local neutrophil responses by G-CSF during pulmonary Pseudomonas aeruginosa infection

Protective effects of Lactobacillus reuteri and Bifidobacterium infantis in murine models for colitis do not involve the vagus nerve

Cathepsin B Is Involved in the Trafficking of TNF-α-Containing Vesicles to the Plasma Membrane in Macrophages

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