Cited by 531Inflammasome and immune disordersImmune Response and InflammationIL-33, ST2, and ILC Pathways

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Inflammasome Components NALP 1 and 3 Show Distinct but Separate Expression Profiles in Human Tissues Suggesting a Site-specific Role in the Inflammatory Response

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Kummer, J. Alain, Broekhuizen, Roel, Everett, Helen, Agostini, Laetitia, Kuijk, Loes, Martinon, Fabio, Bruggen, Robin van, Tschopp, Jürg·2007·Journal of Histochemistry & Cytochemistry

DOI 10.1369/jhc.6a7101.2006

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Abstract

Several autoinflammatory disorders such as Muckle-Wells syndrome are characterized by mutations in the NALP3/cryopyrin gene. NALP3 and NALP1 proteins can assemble to inflammasomes that activate caspase-1, resulting in the processing of proinflammatory cytokines IL-1β and IL-18. The present study was designed to determine which cells and tissues express NALP1 and NALP3. Monoclonal antibodies were developed and their use revealed distinct distribution profiles of NALP1 and NALP3. Granulocytes, monocytes (very weakly), dendritic cells, and B and T cells all express NALP1 and NALP3. Highest levels of NALP1 are found in T cells and Langerhans cells. Furthermore, NALP1 is present in glandular epithelial structures such as stomach, gut, lung, and, surprisingly, in neurons and testis. In contrast to NALP1, NALP3 shows a more restricted tissue distribution with expression mainly in non-keratinizing epithelia in the oropharynx, esophagus, and ectocervix. Moreover, NALP3 expression is found in the urothelial layer in the bladder. Likewise, a difference in subcellular distribution between NALP1 and NALP3 is observed because NALP1 is localized mainly in the nucleus, whereas NALP3 is predominantly cytoplasmic. We propose that the presence of NALP3 in epithelial cells lining the oral and genital tracts allows the rapid sensing of invading pathogens, thereby triggering an innate immune response.

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The Inflammasome
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Self-citation
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Self-citation
Cryopyrin activates the inflammasome in response to toxins and ATP
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Self-citation
Mutation of a new gene encoding a putative pyrin-like protein causes familial cold autoinflammatory syndrome and Muckle–Wells syndrome
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Background
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A narrative review of positive regulation of NLRP3 inflammasome in rheumatoid arthritis.
Zhuang, Y.-P., Wang, H., Su, J., Zhang, J., Wang, Q., Chen, Y.-N., & Che, H. (2021) · Annals of Palliative Medicine · doi:10.21037/apm-21-3472 · Cited by 15
“NLRP3 inflammasome mainly exists in macrophages, neutrophils, and other immune cells, and is a complex multi-protein complex (22).”
Background
Mitochondrial Impairment in Oligodendroglial Cells Induces Cytokine Expression and Signaling
Scheld, M., Fragoulis, A., Nyamoya, S., Zendedel, A., Denecke, B., Krauspe, B., Teske, N., Kipp, M., Beyer, C., & Clarner, T. (2019) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1236-6 · Cited by 17
Dysregulated production of interleukin-1β upon activation of the NLRP3 inflammasome in patients with familial Mediterranean fever
Repa, A., Bertsias, G. K., Petraki, E., Choulaki, C., Vassou, D., Kambas, K., Boumpas, D. T., Goulielmos, G. N., & Sidiropoulos, P. I. (2015) · Human Immunology · doi:10.1016/j.humimm.2015.06.007 · Cited by 17
The Organogermanium Compound 3-(Trihydroxygermyl) Propanoic Acid (THGP) Suppresses Inflammasome Activation Via Complexation with ATP
Azumi, J., Shimada, Y., Takeda, T., Aso, H., & Nakamura, T. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113364 · Cited by 16
“NLRP3, which is a major inflammasome component, is expressed in cells such as macrophages, keratinocytes, and osteoblasts [3].”
Inhibition of NLRP3 alleviates calcium oxalate crystal-induced renal fibrosis and crystal adhesion
Xu, Y., Li, G., Liu, W., Ge, D., Hao, Z., & Wang, W. (2025) · Urolithiasis · doi:10.1007/s00240-025-01716-1 · Cited by 16
“Additionally, this molecular complex is functionally expressed in various mesenchymal-derived cell populations, including fibroblasts, bone-forming osteoblasts, and epidermal keratinocytes [10–13].”
Prostate inflammation: A brief review
Ho, D. (2017) · Urological Science · doi:10.1016/j.urols.2017.04.003 · Cited by 16
The analgesic effect of propofol associated with the inhibition of hypoxia inducible factor and inflammasome in complex regional pain syndrome
Hsiao, H., Liu, Y., Wang, J. C.-F., Liu, Y., & Liu, Y. (2019) · Journal of Biomedical Science · doi:10.1186/s12929-019-0576-z · Cited by 16
Soluble β-amyloid impaired the GABA inhibition by mediating KCC2 in early APP/PS1 mice
Zhou, Y., Cheng, Y., Li, Y., Ma, J., Wu, Z., Chen, Y., Mei, J., & Chen, M. (2021) · BioScience Trends · doi:10.5582/bst.2021.01245 · Cited by 17
“Synaptic failure is an early pathological feature of AD (52), including GABAergic activity (53). γ-aminobutyric acid (GABA), which a principle inhibitory neurotransmitter in the mammalian central nervous system (CNS)mediates synaptic inhibition by acting on GABAA and GABAB receptors (GABAAR, GABABR) (22,54).”
Background
Biological and therapeutic significance of targeting NLRP3 inflammasome in the brain and the current efforts to develop brain-penetrant inhibitors
Kaur, B., Biby, S., Namme, J. N., More, S., Xu, Y., & Zhang, S. (2024) · Advances in pharmacology · doi:10.1016/bs.apha.2024.10.004 · Cited by 15
Apurinic/apyrimidinic endonuclease 1/reduction-oxidation effector factor-1 (APE1) regulates the expression of NLR family pyrin domain containing 3 (NLRP3) inflammasome through modulating transcription factor NF-κB and promoting the secretion of inflammatory mediators in macrophages
Tang, Z., Wang, Y., Wan, Y., Xie, Y., Li, S., Tao, D., Wang, C., Wu, Y., & Sui, J.-D. (2021) · Annals of Translational Medicine · doi:10.21037/atm-20-7752 · Cited by 15
“It has been found that NLR family pyrin domain containing 1 (NLRP1) and 3 (NLRP3) are widely expressed in tissues and cells of the whole body, and a high expression in the monocyte macrophage system (6).”
Background
The E3 ubiquitin ligase RNF31 mediates the development of ulcerative colitis by regulating NLRP3 inflammasome activation
Wang, P., Tang, C., Li, J., Huang, X., Jin, R., Yin, F., Liu, Z., Chen, Y., & Zeng, C. (2023) · International Immunopharmacology · doi:10.1016/j.intimp.2023.111194 · Cited by 14
Genetic polymorphism in an inflammasome component, cervical mycoplasma detection and female infertility in women undergoing in vitro fertilization
Witkin, S. S., Bierhals, K., Linhares, I. M., Normand, N., Dieterle, S., & Neuer, A. (2010) · Journal of Reproductive Immunology · doi:10.1016/j.jri.2009.11.005 · Cited by 15
Preventive Effect of Daiokanzoto (TJ-84) on 5-Fluorouracil-Induced Human Gingival Cell Death through the Inhibition of Reactive Oxygen Species Production
Yoshida, K., Yoshioka, M., Okamura, H., Moriyama, S., Kawazoe, K., Grenier, D., & Hinode, D. (2014) · PLoS ONE · doi:10.1371/journal.pone.0112689 · Cited by 14
Expression and Cell Type-specific Localization of Inflammasome Sensors in the Spinal Cord of SOD1(G93A) Mice and Sporadic Amyotrophic lateral sclerosis Patients
Hummel, C., Leylamian, O., Pösch, A., Weis, J., Aronica, E., Beyer, C., & Johann, S. (2021) · Neuroscience · doi:10.1016/j.neuroscience.2021.03.023 · Cited by 15
Non-coding RNAs: The key regulators in NLRP3 inflammasome-mediated inflammatory diseases
Feng, X., Luo, D., Wei, G., Zhan, F., Hua, F., & Xu, G. (2021) · International Immunopharmacology · doi:10.1016/j.intimp.2021.108105 · Cited by 13
Strategies targeting IL-33/ST2 axis in the treatment of allergic diseases
Li, W., Liu, M., & Chu, M. (2023) · Biochemical Pharmacology · doi:10.1016/j.bcp.2023.115911 · Cited by 14
Inflammasomes in epithelial innate immunity: front line warriors
Robinson, K. S., & Boucher, D. (2024) · FEBS Letters · doi:10.1002/1873-3468.14848 · Cited by 12
Molecular Mechanism of NLRP3 Inflammasome in Inflammatory Diseases and Tumors
Gong, L., Zhou, H., Zhao, Q., Xu, N., Huang, F., Su, L., & Li, W. (2025) · Immunity Inflammation and Disease · doi:10.1002/iid3.70213 · Cited by 13
“…caspase ‐ 1 via CARD ‐ CARD interactions, by linking the NLRP3 receptor protein to the Caspase ‐ 1 effector protein, the activation of Caspase ‐ 1 is promoted [27]., which then promotes IL ‐ 1 β and IL ‐ 18 maturation (Figure 1), inducing inflammation and even cell death known as pyroptosis [28].”
Rôle de l’inflammasome dans les pathologies cardiovasculaires
Connat, J.-L. (2011) · Annales de Cardiologie et d'Angéiologie · doi:10.1016/j.ancard.2010.07.011 · Cited by 12
Association of Nod‐like receptor protein‐1 (rs2670660) and Toll‐like receptor‐4 (rs4986790) with non‐segmental vitiligo: A case–control study in South Indian population
Rajendiran, K. S., Rajappa, M., Chandrashekar, L., & Thappa, D. M. (2019) · International Journal of Immunogenetics · doi:10.1111/iji.12429 · Cited by 10
“TA B L E 7 Logistic regression analysis of association between TLR‐4 (rs4986790) genotype and phenotypes of NSV NLRP‐1 (Kummer et al., 2007).”
Method
Tissue-selective alternate promoters guide NLRP6 expression
Bracey, N. A., Platnich, J. M., Lau, A. N., Chung, H., Hyndman, M. E., MacDonald, J. A., Chun, J., Beck, P. L., Girardin, S. E., Gordon, P. M. K., et al. (2020) · Life Science Alliance · doi:10.26508/lsa.202000897 · Cited by 12
“For example, NLRP1 and NLRP3 protein are expressed in PBMCs, macrophages, lymphocytes, and dendritic cells (Kummer et al, 2007). cDNA pro ﬁ ling of various tissues has revealed even more diverse patterns of expression though, with many NLRs and regulatory genes showing almost uniform expression…”
Chronic mild stress-induced anhedonia in rats is coupled with the upregulation of inflammasome sensors: a possible involvement of NLRP1
Özkartal, C. Ş., Arıcıoğlu, F., Tüzün, E., & Küçükali, C. İ. (2018) · Psychiatry and Clinical Psychopharmacology · doi:10.1080/24750573.2018.1426694 · Cited by 12
“NLRP1 is mainly presented in neurons, whereas NLRP3 is mostly located in microglia [25,50].”
Background
New insights into the immunologic role of oligodendrocyte lineage cells in demyelination diseases
Li, H., Chen, Y., Niu, J., & Yi, C. (2022) · Journal of Biomedical Research · doi:10.7555/jbr.36.20220016 · Cited by 10
“IFN-γ: interferon-gamma; IL-18: interleukin-18; CXCL10: C-X-C motif chemokine ligand 10; CCL3: C-C motif chemokine ligand 3; CCL5: C-C motif chemokine ligand 5; OPCs: oligodendrocyte precursor cells; OLs: oligodendrocytes; MHC Ⅰ/Ⅱ: major histocompatibilitycomplex class Ⅰ/Ⅱ; CD273/274: cluster of differentiation 273/27…”
BackgroundInfluential
Yersinia deploys type III-secreted effectors to evade caspase-4 inflammasome activation in human cells
Zhang, J., Brodsky, I. E., & Shin, S. (2023) · mBio · doi:10.1128/mbio.01310-23 · Cited by 11
“However, studies of human IECs found that NLRP3 does not play a role in inflammasome activation in response to Salmonella infection, potentially due to very low levels of NLRP3 expres sion in human IECs as compared to human macrophages (49, 93, 94).”
BackgroundResult
Canonical Inflammasomes
Leal, V. N. C., & Pontillo, A. (2023) · Methods in molecular biology · doi:10.1007/978-1-0716-3350-2_1 · Cited by 10
Protective effects of ginsenoside Rg1 on neuronal senescence due to inhibition of NOX2 and NLRP1 inflammasome activation in SAMP8 mice
Chen, Y., Ding, S., Zhang, H., Sun, Z., Shen, X., Sun, L., Yin, Y., Qun, S., & Li, W. (2019) · Journal of Functional Foods · doi:10.1016/j.jff.2019.103713 · Cited by 10
Supramolecular organizing centers at the interface of inflammation and neurodegeneration
Sušjan, P., Ramuta, T. Ž., Boršić, E., Orehek, S., & Hafner‐Bratkovič, I. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.940969 · Cited by 11
“In the CNS, NLRP1 is primarily expressed by pyramidal neurons and oligodendrocytes (204).”
Background
An additional piece in the puzzle of neutrophil‐derived IL‐1β: The NLRP3 inflammasome
Tamassia, N., Zimmermann, M., & Cassatella, M. A. (2012) · European Journal of Immunology · doi:10.1002/eji.201242399 · Cited by 10
Mechanism of inflammasomes in cancer and targeted therapies
Gu, Q., Zou, J., Zhou, Y. Y., & Deng, Q. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1133013 · Cited by 10
“NLRP3 was found to be expressed in both immune cells and epithelial cells of colon cancer, manifesting that NLRP3 inflammasomes are involved in the formation of CRC (64).”
Background
Understanding the interplay between psoriatic arthritis and gout: “Psout”
Sherri, A., Mortada, M. M., Makowska, J. S., Sokołowska, M., & Lewandowska‐Polak, A. (2024) · Rheumatology International · doi:10.1007/s00296-024-05729-8 · Cited by 9
A short history of the atrial NLRP3 inflammasome and its distinct role in atrial fibrillation
Poppenborg, T., Saljic, A., Bruns, F., Abu-Taha, I., Dobrev, D., & Fender, A. C. (2025) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2025.02.011 · Cited by 11
Rescuing fertility during COVID-19 infection: exploring potential pharmacological and natural therapeutic approaches for comorbidity, by focusing on NLRP3 inflammasome mechanism.
Hosseini, E., Kohan‐Ghadr, H., Bazrafkan, M., Amorim, C. A., Askari, M., Zakeri, A., Mousavi, S. N., Kafaeinezhad, R., Afradiasbagharani, P., Esfandyari, S., et al. (2023) · Journal of Assisted Reproduction and Genetics · doi:10.1007/s10815-023-02768-1 · Cited by 9
“NLRP3 inflammasome is one of the most studied mechanisms in innate immune cells, such as macrophages, neutrophils, dendritic cells [38–40], and tissues [41, 42].”
Background
GENETIC VARIATIONS IN NALP1 MRNA EXPRESSIONS IN HUMAN VITILIGO
Deo, S., Bhagat, A., & Shah, R. (2011) · Indian Journal of Dermatology · doi:10.4103/0019-5154.82478 · Cited by 9
“[8] NALP1 belongs to a family of cytoplasmic proteins that have been implicated in cell responses to apoptotic and inflammatory stimuli.”
The Role of Inflammasomes in Intestinal Inflammation
Ranson, N., & Eri, R. D. (2013) · American journal of medical and biological research · doi:10.12691/ajmbr-1-3-3 · Cited by 9
“The human NLRP1 protein is expressed in gut epithelial cells, granulocytes, dentritic cells and B cells, with weak expression level in monocytes and high expression levels in T cells and Langerhans cells [35,66].”
Background
Inflammasomes: Role in Disease Pathogenesis and Therapeutic Potential
Garanina, E. E., Martynova, E. V., Ivanov, K., Rizvanov, A. A., & Khaiboullina, S. F. (2020) · Učënye zapiski Kazanskogo universiteta. Seriâ Estestvennye nauki/Učënye zapiski Kazanskogo universiteta. Seriâ Estestvennye nauki/Učenye zapiski Kazanskogo gosudarstvennogo universiteta. Seriâ Estestvennye nauki · doi:10.26907/2542-064x.2020.1.80-111 · Cited by 10
Imbalance in thioredoxin system activates NLRP3 inflammasome pathway in epicardial adipose tissue of patients with coronary artery disease
Shateri, H., Manafi, B., Tayebinia, H., Karimi, J., & Khodadadi, I. (2021) · Molecular Biology Reports · doi:10.1007/s11033-021-06208-0 · Cited by 9
Increased NLRP1 mRNA and Protein Expression Suggests Inflammasome Activation in the Dorsolateral Prefrontal and Medial Orbitofrontal Cortex in Schizophrenia
Španić, E., Vogrinc, D., Fuller, H. R., Horvat, L. L., Mayer, D., Kopić, J., Pintarić, K., Leko, M. B., Pravica, M., Krsnik, Ž., et al. (2024) · Biomolecules · doi:10.3390/biom14030302 · Cited by 8
“Interestingly, while the NLRP3 inflammasome is dominantly expressed in microglia [8,49], a different type of inflammasome, NLRP1, is mostly expressed in the neurons of the central nervous system [50].”
Background
Ferulic Acid Interferes with Radioactive Intestinal Injury Through the DJ-1-Nrf2 and Sirt1-NF-κB-NLRP3 Pathways
Zhang, X., Zhang, H., Huang, M., Mei, Y., Hu, C., Huang, C., Zhang, H., Wei, X., Gao, Y., & Ma, Z. (2024) · Molecules · doi:10.3390/molecules29215072 · Cited by 8
Clinical Potential of Misshapen/NIKs-Related Kinase (MINK) 1—A Many-Sided Element of Cell Physiology and Pathology
Kot, A., Koszewska, D., Ochman, B., & Świętochowska, E. (2024) · Current Issues in Molecular Biology · doi:10.3390/cimb46120826 · Cited by 9
Host–Viral Interactions in the Pathogenesis of Ulcerative Colitis
Bruland, T., Østvik, A. E., Sandvik, A. K., & Hansen, M. D. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms221910851 · Cited by 8
“NLRP1 is expressed by a variety of cell types, including the epithelial structures of the colon [87].”
Background
Early Pregnancy Modulates Expression of the Nod-like Receptor Family in Lymph Nodes of Ewes
Zhao, Z., Li, Y., Cao, J., Fang, H., Zhang, L., & Yang, L. (2022) · Animals · doi:10.3390/ani12233285 · Cited by 8
Hippocampal dipeptidyl peptidase 9 bidirectionally regulates memory associated with synaptic plasticity
Zhao, Y., Wang, S.-Z., Guo, W.-T., Wang, L., Tang, X., Li, J., Xu, L., & Zhou, Q. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.09.031 · Cited by 9
A genetic variant of NLRP1 gene is associated with asbestos body burden in patients with malignant pleural mesothelioma
Crovella, S., de Moura, R. R., Cappellani, S., Celsi, F., Trevisan, E., Schneider, M., Brollo, A., Nicastro, E., Vita, F., Finotto, L., et al. (2017) · Journal of Toxicology and Environmental Health · doi:10.1080/15287394.2017.1416911 · Cited by 8
“In contrast to NLRP3, Kummer et al. (2007) showed for NLRP1 a less restricted tissue distribution with high expression in simple columnar epithelial such as those lining the respiratory tract.”
BackgroundResultInfluential
Hereditary immunologic disorders caused by pyrin and cryopyrin
Hoffman, H. M. (2007) · Current Allergy and Asthma Reports · doi:10.1007/s11882-007-0049-4 · Cited by 8
“Cryopyrin is expressed primarily in myeloid cells including monocytes, macrophages, and neutrophils [34], but also in epithelial cells [ 35 ], synovial fibroblasts [36], and chondrocytes [31].”
Background
Autoinflammatory Disorders, Pain, and Neural Regulation of Inflammation
Chen, M. C., & Meckfessel, M. (2013) · Dermatologic Clinics · doi:10.1016/j.det.2013.04.002 · Cited by 9

Authors: Kummer, J. A., Broekhuizen, R., Everett, H., Agostini, L., Kuijk, L., Martinon, F., Bruggen, R. V., & Tschopp, J.
Affiliations: University Medical Center Utrecht (NL)
University of Lausanne (CH)
Corresponding author: Tschopp, Jürg
ORCID: Kummer, J. Alain
Broekhuizen, Roel
Everett, Helen
Martinon, Fabio
Bruggen, Robin van
Venue: Journal of Histochemistry & Cytochemistry
Publisher: SAGE Publications
Published: 2007-05
Volume: 55
Issue: 5
Pages: 443-452
ISSN: 0022-1554 (ISSN-L)
1551-5044
DOI: 10.1369/jhc.6a7101.2006
OpenAlex: W2043091577
Cited by: 531
References: 34
Citations by year: 2026: 9 · 2025: 20 · 2024: 25 · 2023: 44 · 2022: 24 · 2021: 34 · 2020: 21 · 2019: 40 · 2018: 27 · 2017: 24 · 2016: 23 · 2015: 38 · 2014: 25 · 2013: 36 · 2012: 30
FWCI: 7.60
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: journals.sagepub.com/page/policies/text-and-data-mining-license (tdm)
Locations: Journal of Histochemistry & Cytochemistry (publishedVersion)
PubMed (publishedVersion)
Pure Amsterdam UMC (publishedVersion)
Data Archiving and Networked Services (DANS) (submittedVersion)
IRIS (submittedVersion)
SERVAL (Université de Lausanne) (submittedVersion)
Funders: Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
Life Sciences › Immunology and Microbiology › Immunology › IL-33, ST2, and ILC Pathways
Keywords: NALP1, NLRP3, inflammasome, tissue distribution, autoinflammatory disease, Muckle-Wells syndrome, caspase-1, IL-1β, IL-18, Langerhans cells, epithelial cells, subcellular localization, innate immune response, mucosal immunity
MeSH terms: NLR Proteins, NLR Family, Pyrin Domain-Containing 3 Protein, Antibodies, Monoclonal, Carrier Proteins, Cell Line, Humans, Immunohistochemistry, Inflammation, Organ Specificity, Immunoblotting, Adaptor Proteins, Signal Transducing, Apoptosis Regulatory Proteins

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Inflammasome Components NALP 1 and 3 Show Distinct but Separate Expression Profiles in Human Tissues Suggesting a Site-specific Role in the Inflammatory Response

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