Molecular Mechanism of Tumor Necrosis Factor-α Production in 1→3-β-Glucan (Zymosan)-activated Macrophages

Young, Shih‐Houng; Ye, Jianping; Frazer, David G.; Shi, Xianglin; Castranova, Vince

doi:10.1074/jbc.m101111200

Cited by 137 publications

(107 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Cytokine expression has not been quantified previously 3 d after zymosan injection in this neuritis model, although others have shown increased TNF␣ and IL-1␤ secretion ex vivo from leukocytes recovered from gelfoam at 24 h after perineural zymosan injection . Zymosan activates nuclear factor B by binding to Toll-like receptor 2 (TLR-2) and TLR-6 (Underhill et al, 1999;Young et al, 2001) and likely contributes to pro-inflammatory cytokine gene expression by this mechanism. These cytokines play key roles in the generation of zymosaninduced hypersensitivity, because perisciatic nerve injection of antibodies or receptor antagonists to these cytokines prevents the development of ipsilateral and bilateral hypersensitivity (Twining et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

α2-Adrenoceptor Stimulation Transforms Immune Responses in Neuritis and Blocks Neuritis-Induced Pain

Romero‐Sandoval

McCall²,

Eisenach³

2005

J. Neurosci.

View full text Add to dashboard Cite

Neuropathic pain may be primarily driven by immune responses in peripheral nerves. Peripherally released catecholamines may exacerbate neuropathic pain and also modulate immune responses in a complex and sometimes opposing manner by actions on multiple adrenoceptor subtypes. We showed previously that injection of the ␣2-adrenoceptor agonist clonidine at the site of peripheral nerve injury reduces pain behavior and local tissue pro-inflammatory cytokine content in rats. The current study used a model of acute inflammatory neuritis to test the efficacy and mechanisms of action of ␣2-adrenoceptor stimulation to reduce pain. Zymosan, injected on the sciatic nerve, caused hypersensitivity to mechanical stimuli ipsilateral to injection and contralaterally, so-called mirror image pain. Ipsilateral hypersensitivity was inhibited dose-dependently by perineural injection of clonidine. Zymosan increased leukocyte number at the site of injection 3 d later as well as their content of interleukin 1␣ (IL-1␣), IL-1␤, and IL-6. Perineural clonidine prevented both the increase in leukocyte number and cytokine expression induced by zymosan. Additionally, clonidine reduced the capacity of leukocytes to express pro-inflammatory cytokines as assessed by treatment of cells ex vivo with lipopolysaccharide, whereas no repression of IL-10 production occurred. Clonidine reduced the number of macrophages and lymphocytes as well as their expression of tumor necrosis factor ␣. All of the effects of clonidine were prevented by coadministration of an ␣2A-adrenoceptor-preferring antagonist. These results suggest that ␣2-adrenoceptor stimulation transforms cytokine gene expression, especially in macrophages and lymphocytes from a pro-to an anti-inflammatory profile in the setting of neuritis, likely relieving neuritis-induced pain by this mechanism.

show abstract

Section: Discussionmentioning

confidence: 99%

α2-Adrenoceptor Stimulation Transforms Immune Responses in Neuritis and Blocks Neuritis-Induced Pain

Romero‐Sandoval

McCall²,

Eisenach³

2005

J. Neurosci.

View full text Add to dashboard Cite

show abstract

“…8) The activation of NF-kB is important for the production of inflammatory cytokines such as TNF-a. 28,29) We therefore examined whether the glycosy- Mouse and human Dectin-1 cDNA inserted into a FLAG-tagged expression vector was introduced into HEK293 cells using FuGENE6 transfection reagent. Transfectants were incubated with biotinylated anti-FLAG antibody or biotinylated SPG.…”

Section: Effect Of Dectin-1 Glycosylation On Nf-k Kb Activation In Comentioning

confidence: 99%

Contribution of N-Linked Oligosaccharides to the Expression and Functions of .BETA.-Glucan Receptor, Dectin-1

Kato

Adachi

Ohno

2006

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

“…Zymosan, a commonly studied ␤-glucan source prepared from the nonpathogenic fungus Saccharomyces cerevisiae and other soluble nonpathogenic glucans activate nuclear factor NF-B in cell lines (23)(24)(25)(26). Whether NF-B participates in signaling macrophage inflammatory activation to release TNF␣ following stimulation with cell wall ␤-glucans derived from P. carinii and whether such signaling can be modified pharmacologically are currently unknown.…”

mentioning

confidence: 99%

Pneumocystis carinii Cell Wall β-Glucans Initiate Macrophage Inflammatory Responses through NF-κB Activation

Lebron¹,

Vassallo²,

Puri³

et al. 2003

Journal of Biological Chemistry

110

101

View full text Add to dashboard Cite

␤-Glucans are major structural components of fungi. We have recently reported that the pathogenic fungus Pneumocystis carinii assembles a ␤-glucan-rich cell wall that potently activates alveolar macrophages to release pro-inflammatory cytokines and chemokines. Purified P. carinii ␤-glucans predictably induce both cytokine generation and associated neutrophilic lung inflammation. Herein, we demonstrate that P. carinii ␤-glucaninduced macrophage stimulation results from activation of NF-B. Although analogous to macrophage activation induced by bacterial lipopolysaccharide (LPS), P. carinii ␤-glucan-induced macrophage NF-B activation exhibits distinctly different kinetics, with slower induction and longer duration compared with LPS stimulation. Macrophage activation in response to P. carinii ␤-glucan was also substantially inhibited with the NF-B antagonist pyrrolidine dithiocarbamate. In addition to different kinetics of NF-B activation, P. carinii ␤-glucan and LPS also utilize different receptor systems to induce macrophage activation. Macrophages from Toll-like receptor 4-deficient and wild type mice produced equivalent amounts of tumor necrosis factor ␣ when stimulated with P. carinii ␤-glucan. However, Toll-like receptor 4-deficient macrophages were refractory to stimulation with LPS. In contrast, MyD88-deficient macrophages exhibited a significant (though partial) blunted response to P. carinii ␤-glucan. These data demonstrate that P. carinii ␤-glucan acts as potent inducer of macrophage activation through NF-B utilizing cellular receptors and signaling pathways distinct from LPS.

show abstract

Molecular Mechanism of Tumor Necrosis Factor-α Production in 1→3-β-Glucan (Zymosan)-activated Macrophages

Cited by 137 publications

References 38 publications

α2-Adrenoceptor Stimulation Transforms Immune Responses in Neuritis and Blocks Neuritis-Induced Pain

α2-Adrenoceptor Stimulation Transforms Immune Responses in Neuritis and Blocks Neuritis-Induced Pain

Contribution of N-Linked Oligosaccharides to the Expression and Functions of .BETA.-Glucan Receptor, Dectin-1

Pneumocystis carinii Cell Wall β-Glucans Initiate Macrophage Inflammatory Responses through NF-κB Activation

Contact Info

Product

Resources

About