Serum amyloid A (SAA) activates human mast cells which leads into degradation of SAA and generation of an amyloidogenic SAA fragment

Niemi, Katri; Baumann, Marc; Kovanen, Petri T.; Eklund, Kari K.

doi:10.1016/j.bbadis.2006.01.001

Cited by 20 publications

(23 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, a potential novel pathway for amyloidogenesis can be envisioned: increased levels of SAA during inflammation induce the secretion of cathepsin B from macrophages, resulting in the processing of SAA into amyloidogenic fragments and formation of pathological extracellular amyloid fibrils. Somewhat similar extracellular proteolytic processing of SAA into amyloidogenic fragments has been described for mast cells and mast cell tryptase (6).…”

Section: Discussionmentioning

confidence: 92%

“…Prolonged high SAA levels can lead to amyloidosis, because SAA is the precursor for the amyloid A (AA) protein deposited in tissues in AA-type amyloidosis. SAA was also shown to possess proinflammatory properties [e.g., it can induce the release of cytokines from different cell types, including THP-1 monocytes (3), human neutrophils (4,5), and mast cells (6)]. The levels of SAA, and especially those of the low-density lipoprotein-SAA complex, correlate with the risk for cardiovascular disease (7)(8)(9).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Self Cite

249

225

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 92%

mentioning

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

Self Cite

249

225

View full text Add to dashboard Cite

show abstract

“…Recent evidence has indicated that SAA possesses a number of cytokine‐like properties. It has been reported that SAA stimulates the release of mature IL‐1β from neutrophils, mast cells, macrophages and fibroblasts . However, whether or not SAA can induce IL‐1β production in keratinocytes remains to be investigated.…”

Section: Introductionmentioning

confidence: 99%

Serum amyloid A induces interleukin-1β secretion from keratinocytes via the NACHT, LRR and PYD domains-containing protein 3 inflammasome

Liu

Xie

et al. 2015

Clinical and Experimental Immunology

View full text Add to dashboard Cite

SummaryInterleukin (IL)-1β is now emerging as a critical cytokine in the pathogenesis of T helper type 17 (Th17)-mediated skin diseases, including psoriasis. Psoriatic keratinocytes are a major source of IL-1β; however, the mechanisms triggering IL-1β processing remain unknown. Recently, an acute-phase protein serum amyloid A (SAA) has been identified as a danger signal that triggers inflammasome activation and IL-1β secretion. In this study, we detected increased SAA mRNA and protein expression in psoriatic epidermis.

show abstract

“…However, MCs play multiple roles in diverse diseases, including atherosclerosis [1], ischemia–reperfusion injury [2], autoimmune disorders [3], bladder pain syndrome [4], neuropathic pain [5], autism [6], Alzheimer’s disease [7], and obesity and diabetes mellitus [8]. Massive MC infiltration is found in all stages of lesions in FOP and in HO induced by BMP signaling, especially at early stages of lesions.…”

Section: Introductionmentioning

confidence: 99%

Opioid signaling in mast cells regulates injury responses associated with heterotopic ossification

Kan

Mutso²,

McGuire³

et al. 2013

Inflamm. Res.

View full text Add to dashboard Cite

Introduction Previous studies found that neuron specific enolase promoter (Nse-BMP4) transgenic mice have increased expression of the nociceptive mediator, substance P and exaggerated local injury responses associated with heterotopic ossification (HO). It is of interest great to know the pain responses in these mice and how the opioid signaling is involved in the downstream events such as mast cell (MC) activation. Materials and methods This study utilized a transgenic mouse model of HO in which BMP4 is expressed under the control of the Nse-BMP4. The tactile sensitivity and the cold sensitivity of the mice were measured in a classic inflammatory pain model (carrageenan solution injected into the plantar surface of the left hind paw). The MC activation and the expression profiles of different components in the opioid signaling were demonstrated through routine histology and immunohistochemistry and Western blotting, in the superficial and deep muscle injury models. Results We found that the pain responses in these mice were paradoxically attenuated or unchanged, and we also found increased expression of both Methionine Enkephalin (Met-Enk), and the µ-opioid receptor (MOR). Met-Enk and MOR both co-localized within activated MCs in limb tissues. Further, Nse-BMP4;MOR−/− double mutant mice showed attenuated MC activation and had a significant reduction in HO formation in response to injuries. Conclusions These observations suggest that opioid signaling may play a key role in MC activation and the downstream inflammatory responses associated with HO. In addition to providing insight into the role of MC activation and associated injury responses in HO, these findings suggest opioid signaling as a potential therapeutic target in HO and possibly others disorders involving MC activation.

show abstract

Serum amyloid A (SAA) activates human mast cells which leads into degradation of SAA and generation of an amyloidogenic SAA fragment

Cited by 20 publications

References 37 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

Serum amyloid A induces interleukin-1β secretion from keratinocytes via the NACHT, LRR and PYD domains-containing protein 3 inflammasome

Opioid signaling in mast cells regulates injury responses associated with heterotopic ossification

Contact Info

Product

Resources

About