ALK is required for NLRP3 inflammasome activation in macrophages

Zhang, Bibo; Wei, Wei; Qiu, Jia-Ming

doi:10.1016/j.bbrc.2018.04.226

Cited by 23 publications

(24 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ALK in tumor-associated macrophages promoted tumor metastasis through sustaining inflammation (8). ALK also plays a role in promoting NALP3 (NLR family pyrin domain containing 3) inflammasome activation and pyroptosis in macrophages (9). The conclusions from these studies agree with our conclusion that ALK is a regulator of inflammation and innate immunity in macrophages and monocytes.…”

supporting

confidence: 85%

Response to comment on “ALK is a therapeutic target for lethal sepsis”

Tang

Kang

2018

Sci. Transl. Med.

View full text Add to dashboard Cite

show abstract

supporting

confidence: 85%

Response to comment on “ALK is a therapeutic target for lethal sepsis”

Tang

Kang

2018

Sci. Transl. Med.

View full text Add to dashboard Cite

show abstract

“…ProTECT allows the prediction of high affinity binders (epitopes) to common HLA alleles, with which a nonamer (AQDIYRASY) and two decamer sequences of ALK (MAQDIYRASY and AQDIYRASYY) with high affinities to HLA-B*15:01 were identified. These peptides were then experimentally confirmed to be able to raise CD8+ T-cell recognition using patient PBMC with matched HLA-alleles [38]. Overall, the above studies showed that immunogenic ALK epitopes could be identified against ALK mutant as well as ALK-fusion cancers.…”

Section: Cytotoxic T-cell Responses Against Alk With Epitope Identifimentioning

confidence: 82%

“…In general, inflammasomes can regulate host immune responses and cause human diseases by inducing pyroptosis (proinflammatory programmed cell death) and the release of cytokines such as IL-1β and IL-18. ALK has been shown to regulate and promote activation of NLRP3 inflammasome in macrophages [38]. Using ALK siRNA, and ALK inhibitors, ceritinib and lorlatinib, Zhang et al showed that ALK was capable of regulating both the priming and the sensing steps of pyroptotic cell death in mouse bone marrow-derived macrophages [38].…”

Section: Alk In Inflammasome Activation and Cytokinesmentioning

confidence: 99%

“…ALK has been shown to regulate and promote activation of NLRP3 inflammasome in macrophages [38]. Using ALK siRNA, and ALK inhibitors, ceritinib and lorlatinib, Zhang et al showed that ALK was capable of regulating both the priming and the sensing steps of pyroptotic cell death in mouse bone marrow-derived macrophages [38]. In the priming step of NLRP3 inflammasome formation, ALK mediates NF-kB activation, which then activates LPS-induced NLRP3 transcription.…”

Section: Alk In Inflammasome Activation and Cytokinesmentioning

confidence: 99%

See 1 more Smart Citation

Emerging Roles of ALK in Immunity and Insights for Immunotherapy

Wang

Lui

2020

Cancers

View full text Add to dashboard Cite

Anaplastic lymphoma kinase (ALK) is mostly known for its oncogenic role in several human cancers. Recent evidences clearly indicate new roles of ALK and its genetic aberrations (e.g. gene rearrangements and mutations) in immune evasion, innate and cell-mediated immunity. New ALK-related immunotherapy approaches are demonstrating both preclinical and clinical promises. Here, we provide a timely review on the most updated laboratory and patient-related findings on ALK and immunity, which would grant us important insights for the development of novel ALK immunotherapies for ALK-altered cancers.

show abstract

“…7 ). A known substrate of RPTPβ/ζ, ALK 13 , regulates the activation of STAT3 through modulation of its tyrosine phosphorylation 17 and has been linked to the activation of the inflammasome (NLRP3) in macrophages, which triggers a rapid immune response against pathogen-associated molecular patterns (PAMPs) 25 . However, as it happened in Ptn -Tg mice, treatment with MY10 did not seem to regulate the phosphorylation of STAT3 in the PFC of mice treated with LPS, suggesting that the regulation of LPS-induced microglial response by MY10 is independent of STAT3.…”

Section: Discussionmentioning

confidence: 99%

Role of RPTPβ/ζ in neuroinflammation and microglia-neuron communication

Fernández-Calle

Galán-Llario

Gramage

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Pleiotrophin (PTN) is a cytokine that is upregulated in different neuroinflammatory disorders. Using mice with transgenic PTN overexpression in the brain (Ptn-Tg), we have found a positive correlation between iNos and Tnfα mRNA and Ptn mRNA levels in the prefrontal cortex (PFC) of LPS-treated mice. PTN is an inhibitor of Receptor Protein Tyrosine Phosphatase (RPTP) β/ζ, which is mainly expressed in the central nervous system. We aimed to test if RPTPβ/ζ is involved in the modulation of neuroinflammatory responses using specific inhibitors of RPTPβ/ζ (MY10 and MY33-3). Treatment with MY10 potentiated LPS-induced microglial responses in the mouse PFC. Surprisingly, MY10 caused a decrease in LPS-induced NF-κB p65 expression, suggesting that RPTPβ/ζ may be involved in a novel mechanism of potentiation of microglial activation independent of the NF-κB p65 pathway. MY33-3 and MY10 limited LPS-induced nitrites production and iNos increases in BV2 microglial cells. SH-SY5Y neuronal cells were treated with the conditioned media from MY10/LPS-treated BV2 cells. Conditioned media from non-stimulated and from LPS-stimulated BV2 cells increased the viability of SH-SY5Y cultures. RPTPβ/ζ inhibition in microglial cells disrupted this neurotrophic effect of microglia, suggesting that RPTPβ/ζ plays a role in the neurotrophic phenotype of microglia and in microglia-neuron communication.

show abstract

ALK is required for NLRP3 inflammasome activation in macrophages

Cited by 23 publications

References 31 publications

Response to comment on “ALK is a therapeutic target for lethal sepsis”

Response to comment on “ALK is a therapeutic target for lethal sepsis”

Emerging Roles of ALK in Immunity and Insights for Immunotherapy

Role of RPTPβ/ζ in neuroinflammation and microglia-neuron communication

Contact Info

Product

Resources

About