title: MALT1 Protease Activity Controls the Expression of Inflammatory Genes in Keratinocytes upon Zymosan Stimulation.
abstract: The protease activity of the paracaspase mucosa-associated lymphoid tissue lymphoma translocation gene 1 (MALT1) plays an important role in antigen receptor-mediated lymphocyte activation by controlling the activity of the transcription factor nuclear factor-κB and is thus essential for the expression of inflammatory target genes. MALT1 is not only present in cells of the hematopoietic lineage, but is ubiquitously expressed. Here we report that stimulation with zymosan or Staphylococcus aureus induced MALT1 protease activity in human primary keratinocytes. Inhibition of the Src family of kinases or novel protein kinase C isoforms as well as silencing of CARMA2 or BCL10 interfered with activation of MALT1 protease. Silencing or inhibition of MALT1 protease strongly decreased the expression of important inflammatory genes such as TNFα, IL-17C, CXCL8 and HBD-2. MALT1-inhibited cells were unable to mount an antimicrobial response upon zymosan stimulation or phorbolester/ionomycin treatment, demonstrating a central role of MALT1 protease activity in keratinocyte immunity and suggesting MALT1 as a potential target in inflammatory skin diseases.
authors.affiliation: Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schmitt
authors.affiliation: Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Paula
authors.initials: P
authors.lastname: Grondona
authors.affiliation: Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Tabea
authors.initials: T
authors.lastname: Maier
authors.affiliation: Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Brändle
authors.affiliation: Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Schönfeld
authors.affiliation: Institute of Medical Genetics and Applied Genomics, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Günter
authors.initials: G
authors.lastname: Jäger
authors.affiliation: Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Kosnopfel
authors.affiliation: Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Franziska C
authors.initials: FC
authors.lastname: Eberle
authors.affiliation: Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
authors.affiliation: Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulze-Osthoff
authors.affiliation: Department of Dermatology, Eberhard Karls University of Tuebingen, Tuebingen, Germany.
authors.forename: Amir S
authors.initials: AS
authors.lastname: Yazdi
authors.affiliation: Interfaculty Institute for Biochemistry, Eberhard Karls University of Tuebingen, Tuebingen, Germany. Electronic address: Stephan.Hailfinger@uni-tuebingen.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Hailfinger
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000890:Anti-Infective Agents / Q000737:chemistry; D000074018:B-Cell CLL-Lymphoma 10 Protein; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D020869:Gene Expression Profiling; D020868:Gene Silencing; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000235:genetics*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism; D013211:Staphylococcus aureus; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015054:Zymosan / Q000737:chemistry*; D023083:beta-Defensins / Q000235:genetics / Q000378:metabolism; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000890:Anti-Infective Agents; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; D053468:CARD Signaling Adaptor Proteins; C508606:CXCL8 protein, human; C106641:DEFB4A protein, human; C515925:IL17C protein, human; D020381:Interleukin-17; D016209:Interleukin-8; D008565:Membrane Proteins; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D014409:Tumor Necrosis Factor-alpha; D023083:beta-Defensins; D015054:Zymosan; D019061:src-Family Kinases; D011493:Protein Kinase C; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; C426243:CARD14 protein, human; D006162:Guanylate Cyclase