Oliver P. Skinner, BSc, Julie Jurczyluk, BSc, Paul J

Slides:

Advertisements

Similar presentations

Proinflammatory cytokine–induced and chemical mediator–induced IL-8 expression in human bronchial epithelial cells through p38 mitogen-activated protein.

Advertisements

Differential effects of GLP-1 receptor agonist on foam cell formation in monocytes between non-obese and obese subjects Masashi Tanaka, Yoshiyuki Matsuo,

Hal M. Hoffman, MD, Lori Broderick, MD, PhD

Volume 66, Issue 5, Pages (May 2017)

Immune deficiency caused by impaired expression of nuclear factor-κB essential modifier (NEMO) because of a mutation in the 5′ untranslated region of.

Development of immunologic memory against tetanus toxoid and pertactin antigens from the diphtheria-tetanus-pertussis vaccine in atopic versus nonatopic.

Human circulating group 2 innate lymphoid cells can express CD154 and promote IgE production Laura Maggi, PhD, Gianni Montaini, BSc, Alessio Mazzoni,

Pharmacological inhibition of caspase-8 suppresses inflammation-induced lymphangiogenesis and allograft rejection in the cornea Wenru Su, MD, PhD, Longhui.

Low E-prostanoid 2 receptor levels and deficient induction of the IL-1β/IL-1 type I receptor/COX-2 pathway: Vicious circle in patients with aspirin-exacerbated.

Regulation of inflammasomes by autophagy

Modulation by aspirin of nuclear phospho–signal transducer and activator of transcription 6 expression: Possible role in therapeutic benefit associated.

Thymic stromal lymphopoietin downregulates filaggrin expression by signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated.

Therapy of autoinflammatory syndromes

Defective nuclear entry of hydrolases prevents neutrophil extracellular trap formation in patients with chronic granulomatous disease Susana Romao, PhD,

Volume 8, Issue 2, Pages (July 2014)

Bruton tyrosine kinase mediates TLR9-dependent human dendritic cell activation Vassilios Lougaris, MD, Manuela Baronio, PhD, Massimiliano Vitali, PhD,

Julie M. Caldwell, PhD, Carine Blanchard, PhD, Margaret H

The airway epithelium nucleotide-binding domain and leucine-rich repeat protein 3 inflammasome is activated by urban particulate matter Jeremy A. Hirota,

Targeting Toll-like receptors on dendritic cells modifies the TH2 response to peanut allergens in vitro Pierre Pochard, PhD, Brian Vickery, MD, M. Cecilia.

Estrogen enhances immunoglobulin production by human PBMCs

Reduction of CRKL expression in patients with partial DiGeorge syndrome is associated with impairment of T-cell functions Mauro Giacomelli, PhD, Rajesh.

Hal M. Hoffman, MD, Lori Broderick, MD, PhD

Glycation of a food allergen by the Maillard reaction enhances its T-cell immunogenicity: Role of macrophage scavenger receptor class A type I and II

Autoinflammation: The prominent role of IL-1 in monogenic autoinflammatory diseases and implications for common illnesses Raphaela Goldbach-Mansky, MD,

Differential control of TH1 versus TH2 cell responses by the combination of low-dose steroids with β2-adrenergic agonists Elena Goleva, PhD, Annegret.

Specificity protein 1 is pivotal in the skin’s antiviral response

Pyroptosis Current Biology

Shared and restricted T-cell receptor use is crucial for carbamazepine-induced Stevens- Johnson syndrome Tai-Ming Ko, MS, Wen-Hung Chung, MD, PhD, Chun-Yu.

Cysteinyl leukotriene E4 activates human group 2 innate lymphoid cells and enhances the effect of prostaglandin D2 and epithelial cytokines Maryam Salimi,

Glucosamine promotes chondrogenic phenotype in both chondrocytes and mesenchymal stem cells and inhibits MMP-13 expression and matrix degradation A.

IL-13 desensitizes β2-adrenergic receptors in human airway epithelial cells through a 15-lipoxygenase/G protein receptor kinase 2 mechanism Giusy D.

Mite allergen is a danger signal for the skin via activation of inflammasome in keratinocytes Xiuju Dai, MD, PhD, Koji Sayama, MD, PhD, Mikiko Tohyama,

Integrin α5β1 Activates the NLRP3 Inflammasome by Direct Interaction with a Bacterial Surface Protein Hye-Kyoung Jun, Sung-Hoon Lee, Hae-Ri Lee, Bong-Kyu.

Human mast cell degranulation and preformed TNF secretion require mitochondrial translocation to exocytosis sites: Relevance to atopic dermatitis Bodi.

Bruton tyrosine kinase inhibition: Clinical relevance beyond B cells

IL-13 dampens human airway epithelial innate immunity through induction of IL-1 receptor–associated kinase M Qun Wu, MD, PhD, Di Jiang, BS, Sean Smith,

Interleukin receptor-associated kinase-4 deficiency impairs Toll-like receptor–dependent innate antiviral immune responses Douglas R. McDonald, MD, PhD,

MicroRNA-9 regulates steroid-resistant airway hyperresponsiveness by reducing protein phosphatase 2A activity Jing Jing Li, MS, Hock L. Tay, PhD, Steven.

Inhibition of human B-cell development into plasmablasts by histone deacetylase inhibitor valproic acid Anne-Kathrin Kienzler, MSc, Marta Rizzi, MD,

Hsueh Yang, Gabrielle Curinga, Cecilia M. Giachelli

Fibronectin is a TH1-specific molecule in human subjects

Min Qin, Aslan Pirouz, Myung-Hwa Kim, Stephan R. Krutzik, Hermes J

Defective protein prenylation is a diagnostic biomarker of mevalonate kinase deficiency Marcia A. Munoz, BSc, PhD, Julie Jurczyluk, BSc, Sam Mehr, MBBS,

Min Qin, Aslan Pirouz, Myung-Hwa Kim, Stephan R. Krutzik, Hermes J

Thymic stromal lymphopoietin activity is increased in nasal polyps of patients with chronic rhinosinusitis Deepti R. Nagarkar, PhD, Julie A. Poposki,

An endogenous caspase-11 ligand elicits interleukin-1 release from living dendritic cells by Ivan Zanoni, Yunhao Tan, Marco Di Gioia, Achille Broggi, Jianbin.

Dangerous Liaisons: Mitochondrial DNA Meets the NLRP3 Inflammasome

Fibronectin is a TH1-specific molecule in human subjects

Immune deficiency caused by impaired expression of nuclear factor-κB essential modifier (NEMO) because of a mutation in the 5′ untranslated region of.

Larisa I. Labzin, PhD, Mario A.R. Lauterbach, MSc, Eicke Latz, MD, PhD

Staphylococcal exotoxins are strong inducers of IL-22: A potential role in atopic dermatitis Margarete Niebuhr, MD, Helena Scharonow, MS, Merle Gathmann,

Desiccating stress worsens alkali burn injury by magnifying caspase-8-induced imbalance of NLRP3 and NLRP6 Xia Hua, MD, PhD, Xiaoyong Yuan, MD, PhD,

Connective tissue growth factor expression is regulated by histamine in lung fibroblasts: Potential role of histamine in airway remodeling Steffen Kunzmann,

Olea europaea pollen lipids activate invariant natural killer T cells by upregulating CD1d expression on dendritic cells Beatriz Abós-Gracia, BSc, Manuel.

Enhanced CD46-induced regulatory T cells suppress allergic inflammation after Dermatophagoides pteronyssinus–specific immunotherapy Yi-Giien Tsai, MD,

Prostaglandin D2 activates group 2 innate lymphoid cells through chemoattractant receptor-homologous molecule expressed on TH2 cells Luzheng Xue, PhD,

Human Monocytes Engage an Alternative Inflammasome Pathway

Volume 39, Issue 1, Pages (July 2013)

IL-13 dampens human airway epithelial innate immunity through induction of IL-1 receptor–associated kinase M Qun Wu, MD, PhD, Di Jiang, BS, Sean Smith,

Activation of human mast cells through the platelet-activating factor receptor Naoki Kajiwara, PhD, Tomomi Sasaki, BSc, Peter Bradding, DM, Glenn Cruse,

P38 Mitogen-activated protein kinase–induced glucocorticoid receptor phosphorylation reduces its activity: Role in steroid-insensitive asthma Elvis Irusen,

Fig. 2. Spontaneous inflammasome activation by pyrin S242R.

D-type prostanoid receptor enhances the signaling of chemoattractant receptor– homologous molecule expressed on TH2 cells Miriam Sedej, MSc, Ralf Schröder,

Staphylococcus aureus α-toxin modulates skin host response to viral infection Lianghua Bin, PhD, Byung Eui Kim, MD, Anne Brauweiler, PhD, Elena Goleva,

Volume 25, Issue 9, Pages e5 (November 2018)

Siobhan O. Burns, MD, PhD, Helen L

Julie Negri, BA, S. Brandon Early, BA, John W

Bleomycin hydrolase downregulation in lesional skin of adult atopic dermatitis patients is independent of FLG gene mutations Laurence Pellerin, PhD,

Anti-inflammatory and corticosteroid-enhancing actions of vitamin D in monocytes of patients with steroid-resistant and those with steroid-sensitive asthma

The Activity of Caspase-1 Is Increased in Lesional Psoriatic Epidermis

Presentation transcript:

Lack of protein prenylation promotes NLRP3 inflammasome assembly in human monocytes Oliver P. Skinner, BSc, Julie Jurczyluk, BSc, Paul J. Baker, PhD, Seth L. Masters, PhD, Alicia G. Rios Wilks, BSc, Misaki S. Clearwater, BSc, Avril A.B. Robertson, PhD, MChem, GCHEd, Kate Schroder, PhD, Sam Mehr, MBBS, BMedSci, FRCPA, FRACP, Marcia A. Munoz, PhD, Michael J. Rogers, PhD Journal of Allergy and Clinical Immunology Volume 143, Issue 6, Pages 2315-2317.e3 (June 2019) DOI: 10.1016/j.jaci.2019.02.013 Copyright © 2019 The Authors Terms and Conditions

Fig 1 A-D, SIM pretreatment enhanced LPS-induced IL-1β release (Fig 1, A), ASC speck formation (Fig 1, B), caspase-1 activity (Fig 1, C), and IL-18 release (Fig 1, D), all of which were restored to control levels in the presence of GGOH. Data in Fig 1, D, are from 1 representative experiment of more than 4 (IL-1β) or 2 (IL-18) experiments. E, GGOH prevented SIM-induced accumulation of unprenylated Rab (uRabs) and unprenylated Rap1A (uRap1A) proteins. F, Doxycycline-inducible knockout of NLRP3, pyrin, or caspase-1 proteins in Cas9-expressing THP-1 cells. KO, Knockout. G, Lack of NLRP3 or CASP1, but not MEFV (pyrin), abolished LPS-induced IL-1β release and prevented the enhancing effect of SIM. H and I, MCC950 inhibited LPS-induced caspase-1 activity (Fig 1, H) and IL-1β release (Fig 1, I) and blocked the enhancing effect of SIM in THP-1 cells. J, After stimulation with LPS/nigericin, IL-1β release was increased in PBMCs from a patient with MKD compared with PBMCs from each unaffected parent, and MCC950 completely abolished IL-1β production in all PBMC cultures. K, SIM pretreatment enhanced formation of ASC specks and IL-1β release after Pam3CSK4 stimulation in THP-1 cells. Values represent either means ± SDs from 3 independent experiments (**P < .01, ***P < .001, and ****P < .0001) or are representative of at least 3 separate experiments. Journal of Allergy and Clinical Immunology 2019 143, 2315-2317.e3DOI: (10.1016/j.jaci.2019.02.013) Copyright © 2019 The Authors Terms and Conditions

Fig E1 A and B, SIM treatment did not affect THP-1 cell viability (Trypan Blue exclusion; Fig E1, A) but caused a concentration-dependent accumulation of unprenylated Rab (uRabs) and Rap1A (uRap1A) GTPases (Fig E1, B). Endogenous 75-kDa biotinylated protein was used as a loading control. C, SIM treatment enhanced LPS-induced pyroptosis (propidium iodide [PI] uptake), and pyroptosis was restored to normal levels by means of GGOH addition and abolished by MCC950. D and E, Doxycycline-induced NLRP3 deletion abolished ASC speck formation (Fig E1, D) and caspase-1 activity (Fig E1, E) upon LPS stimulation (nigericin treatment was used as a positive control). F, CASP4 and CASP5 were not required for the enhancing effects of SIM on IL-1β release after LPS stimulation. Loss of caspase-4 was confirmed by using western blotting. G, Blocking [K+] efflux with 50 mmol/L extracellular [K+] abolished LPS-induced IL-1β release in the presence or absence of SIM. H, The reactive oxygen species scavenger butylated hydroxyanisole (BHA) prevented SIM-enhanced IL-1β release after LPS stimulation. I, MCC950 inhibited LPS-stimulated IL-1β release from cells pretreated with SIM or GGTI-298. **P < .01 and ****P < .0001. Values in all figures are means ± SDs of triplicate wells, with the exception of Fig E1, H, showing means of duplicate wells. All data shown are representative of 3 independent experiments. Journal of Allergy and Clinical Immunology 2019 143, 2315-2317.e3DOI: (10.1016/j.jaci.2019.02.013) Copyright © 2019 The Authors Terms and Conditions

Fig E2 Pretreatment of THP-1 cells with SIM did not enhance mRNA or protein expression of inflammasome components/substrates. A, Quantitative PCR analysis of mRNA expression of genes encoding IL-1β, IL-18, NLRP3, pyrin (MEFV), ASC, and caspase-1 in control cells (black lines) or SIM-pretreated cells (red lines) for up to 6 hours after LPS stimulation. Values are means ± SDs from 3 independent experiments. B, Western blots showing protein levels of pro–IL-1β, NLRP3, pyrin, and pro–caspase-1 in control or SIM-pretreated cells for up to 4 hours after LPS stimulation. Zero hours represents control or SIM pretreatment before LPS stimulation; β-actin was used as a loading control. Blots are representative of 3 independent experiments. Journal of Allergy and Clinical Immunology 2019 143, 2315-2317.e3DOI: (10.1016/j.jaci.2019.02.013) Copyright © 2019 The Authors Terms and Conditions