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

J. Alain Kummer ¹, Roel Broekhuizen ¹, Helen Everett ¹, Laetitia Agostini ¹, Loes Kuijk ¹, Fabio Martinon ¹, Robin van Bruggen ¹ and Jürg Tschopp ^1*

¹ Department of Pathology (JAK,RB) and Department of Immunology (LK), University Medical Center Utrecht, Utrecht, The Netherlands; and Department of Biochemistry, University of Lausanne, BIL Biomedical Research Center, Epalinges, Switzerland (HE,LA,FM,RVB,JT)

^* To whom correspondence should be addressed. E-mail: jurg.tschopp{at}unil.ch.

Submitted on September 26, 2006
Accepted on 1 December 2006

	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 the pro-inflammatory cytokines IL-1 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, 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, since NALP1 is mainly localized in the nucleus while NALP3 is predominantly cytoplasmic. We propose that the presence of NALP3 in epithelial cells lining the oral and genital tract allows the rapid sensing of invading pathogens, thereby triggering an innate immune response.

Key Words: autoinflammatory disease, inflammation, mucosa

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Grandemange, S. Soler, and I. Touitou Expression of the familial Mediterranean fever gene is regulated by nonsense-mediated decay Hum. Mol. Genet., December 15, 2009; 18(24): 4746 - 4755. [Abstract] [Full Text] [PDF]

				N. Sasi, M. Hwang, J. Jaboin, I. Csiki, and B. Lu Regulated cell death pathways: New twists in modulation of BCL2 family function Mol. Cancer Ther., June 1, 2009; 8(6): 1421 - 1429. [Abstract] [Full Text] [PDF]

				F. A. Sharp, D. Ruane, B. Claass, E. Creagh, J. Harris, P. Malyala, M. Singh, D. T. O'Hagan, V. Petrilli, J. Tschopp, et al. Uptake of particulate vaccine adjuvants by dendritic cells activates the NALP3 inflammasome PNAS, January 20, 2009; 106(3): 870 - 875. [Abstract] [Full Text] [PDF]

				P I Sidiropoulos, G Goulielmos, G K Voloudakis, E Petraki, and D T Boumpas Inflammasomes and rheumatic diseases: evolving concepts Ann Rheum Dis, October 1, 2008; 67(10): 1382 - 1389. [Abstract] [Full Text] [PDF]

				A. Kastbom, D. Verma, P. Eriksson, T. Skogh, G. Wingren, and P. Soderkvist Genetic variation in proteins of the cryopyrin inflammasome influences susceptibility and severity of rheumatoid arthritis (The Swedish TIRA project) Rheumatology, April 1, 2008; 47(4): 415 - 417. [Abstract] [Full Text] [PDF]

				J. P. de Rivero Vaccari, G. Lotocki, A. E. Marcillo, W. D. Dietrich, and R. W. Keane A Molecular Platform in Neurons Regulates Inflammation after Spinal Cord Injury J. Neurosci., March 26, 2008; 28(13): 3404 - 3414. [Abstract] [Full Text] [PDF]

				S. Farasat, I. Aksentijevich, and J. R. Toro Autoinflammatory Diseases: Clinical and Genetic Advances Arch Dermatol, March 1, 2008; 144(3): 392 - 402. [Abstract] [Full Text] [PDF]

				J. M. Wilmanski, T. Petnicki-Ocwieja, and K. S. Kobayashi NLR proteins: integral members of innate immunity and mediators of inflammatory diseases J. Leukoc. Biol., January 1, 2008; 83(1): 13 - 30. [Abstract] [Full Text] [PDF]

				J. H. F. Pedra, F. S. Sutterwala, B. Sukumaran, Y. Ogura, F. Qian, R. R. Montgomery, R. A. Flavell, and E. Fikrig ASC/PYCARD and Caspase-1 Regulate the IL-18/IFN-{gamma} Axis during Anaplasma phagocytophilum Infection J. Immunol., October 1, 2007; 179(7): 4783 - 4791. [Abstract] [Full Text] [PDF]

				S. Seshadri, M. D. Duncan, J. M. Hart, M. A. Gavrilin, and M. D. Wewers Pyrin Levels in Human Monocytes and Monocyte-Derived Macrophages Regulate IL-1beta Processing and Release J. Immunol., July 15, 2007; 179(2): 1274 - 1281. [Abstract] [Full Text] [PDF]

Guidelines | Subscriptions | About | exPRESS - Current - Archive | Business Information | Contact

The Journal of Histochemistry & Cytochemistry is owned, published, and licensed by The Histochemical Society © 2006