Serum amyloid A induces G-CSF expression and neutrophilia via Toll-like receptor 2

He, Rong; Zhou, Jian; Hanson, Crystal Z.; Chen, Jia; Cheng, Ni; Ye, Richard D.

doi:10.1182/blood-2008-03-139923

Cited by 152 publications

(147 citation statements)

References 53 publications

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“…2). These findings are consistent with previous reports, which used TLR2-and TLR4-deficient mice to show that SAA can activate TLR2 and TLR4 receptors (35)(36)(37)(38). The scavenger receptor CD36 has been recently shown to function as a receptor for SAA and to mediate the expression of IL-8 in response to SAA (39).…”

Section: Discussionsupporting

confidence: 82%

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Serum Amyloid A Activates the NLRP3 Inflammasome via P2X7 Receptor and a Cathepsin B-Sensitive Pathway

Niemi

Teirilä

Lappalainen

et al. 2011

The Journal of Immunology

250

225

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Serum amyloid A (SAA) is an acute-phase protein, the serum levels of which can increase up to 1000-fold during inflammation. SAA has a pathogenic role in amyloid A-type amyloidosis, and increased serum levels of SAA correlate with the risk for cardiovascular diseases. IL-1β is a key proinflammatory cytokine, and its secretion is strictly controlled by the inflammasomes. We studied the role of SAA in the regulation of IL-1β production and activation of the inflammasome cascade in human and mouse macrophages, as well as in THP-1 cells. SAA could provide a signal for the induction of pro–IL-1β expression and for inflammasome activation, resulting in secretion of mature IL-1β. Blocking TLR2 and TLR4 attenuated SAA-induced expression of IL1B, whereas inhibition of caspase-1 and the ATP receptor P2X7 abrogated the release of mature IL-1β. NLRP3 inflammasome consists of the NLRP3 receptor and the adaptor protein apoptosis-associated speck-like protein containing CARD (a caspase-recruitment domain) (ASC). SAA-mediated IL-1β secretion was markedly reduced in ASC−/− macrophages, and silencing NLRP3 decreased IL-1β secretion, confirming NLRP3 as the SAA-responsive inflammasome. Inflammasome activation was dependent on cathepsin B activity, but it was not associated with lysosomal destabilization. SAA also induced secretion of cathepsin B and ASC. In conclusion, SAA can induce the expression of pro–IL-1β and activation of the NLRP3 inflammasome via P2X7 receptor and a cathepsin B-sensitive pathway. Thus, during systemic inflammation, SAA may promote the production of IL-1β in tissues. Furthermore, the SAA-induced secretion of active cathepsin B may lead to extracellular processing of SAA and, thus, potentially to the development of amyloid A amyloidosis.

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Section: Discussionsupporting

confidence: 82%

“…SAA has been shown to interact with several cell-surface receptors, including formylpeptide receptor-like 1 (FPRL1) (5,33,34), TLR4 (35), TLR2 (36)(37)(38), and the scavenger receptor CD36 (39). The ability of SAA and TLR4 agonist LPS to induce IL1B expression was studied first.…”

Section: Saa Induces Synthesis Of Pro-il-1b Through Tlr2 and Tlr4mentioning

confidence: 99%

Serum Amyloid A Activates the NLRP3 Inflammasome via P2X7 Receptor and a Cathepsin B-Sensitive Pathway

Niemi

Teirilä

Lappalainen

et al. 2011

The Journal of Immunology

250

225

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“…In addition to FPR2, several other targets have been reported as specific receptors for SAA, including receptor for advanced glycation end products (Yan et al, 2000), the HDL receptor, scavenger receptor class B type I (Cai et al, 2005), CLA-1 (CD36 and LIMPII analogous-1), human orthologue of the Scavenger Receptor Class B Type I (Baranova et al, 2005), P2X7 (Christenson et al, 2008), TLR4 (Sandri et al, 2008), and TLR2 (He et al, 2009). Because we found that SAA stimulated CCL2 production via a PTX-insensitive pathway, we confirmed a role for FPR2 in SAA-induced cellular signaling in HUVECs.…”

Section: Discussionmentioning

confidence: 99%

A pertussis toxin sensitive G-protein-independent pathway is involved in serum amyloid A-induced formyl peptide receptor 2-mediated CCL2 production

et al. 2010

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“…Saa3, is a major acute-phase protein that can act as a chemoattractant for phagocytes (35) and recently was shown to promote Th17-mediated allergic asthma through the activation of the NLRP3 inflammasome complex (36). Our data showed that this gene was significantly upregulated following Flu infection, with an additional 2-fold increase following HDM exposure during the EP that was sustained through the LP, where we observed a 5-fold difference in expression level between Flu-and Flu+HDM-treated mice (Tables VI, VII).…”

Section: Discussionmentioning

confidence: 99%

Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights

Al-Garawi

Husain

Ilieva

et al. 2012

The Journal of Immunology

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Respiratory viral infections have been associated with an increased incidence of allergic asthma. However, the mechanisms by which respiratory infections facilitate allergic airway disease are incompletely understood. We previously showed that exposure to a low dose of house dust mite (HDM) resulted in enhanced HDM-mediated allergic airway inflammation, and, importantly, marked airway hyperreactivity only when allergen exposure occurred during an acute influenza A infection. In this study, we evaluated the impact of concurrent influenza infection and allergen exposure at the genomic level, using whole-genome microarray. Our data showed that, in contrast to exposure to a low dose of HDM, influenza A infection led to a dramatic increase in gene expression, particularly of TLRs, C-type lectin receptors, several complement components, as well as FcεR1. Additionally, we observed increased expression of a number of genes encoding chemokines and cytokines associated with the recruitment of proinflammatory cells. Moreover, HDM exposure in the context of an influenza A infection resulted in the induction of unique genes, including calgranulin A (S100a8), an endogenous damage-associated molecular pattern and TLR4 agonist. In addition, we observed significantly increased expression of serum amyloid A (Saa3) and serine protease inhibitor 3n (Serpina3n). This study showed that influenza infection markedly increased the expression of multiple gene classes capable of sensing allergens and amplifying the ensuing immune-inflammatory response. We propose that influenza A infection primes the lung environment in such a way as to lower the threshold of allergen responsiveness, thus facilitating the emergence of a clinically significant allergic phenotype.

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Serum amyloid A induces G-CSF expression and neutrophilia via Toll-like receptor 2

Cited by 152 publications

References 53 publications

Serum Amyloid A Activates the NLRP3 Inflammasome via P2X7 Receptor and a Cathepsin B-Sensitive Pathway

Serum Amyloid A Activates the NLRP3 Inflammasome via P2X7 Receptor and a Cathepsin B-Sensitive Pathway

A pertussis toxin sensitive G-protein-independent pathway is involved in serum amyloid A-induced formyl peptide receptor 2-mediated CCL2 production

Shifting of Immune Responsiveness to House Dust Mite by Influenza A Infection: Genomic Insights

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