Interleukin-6-interleukin-11 receptor chimeras reveal ionomycin-induced proteolysis beyond ADAM10.


Journal

FEBS letters
ISSN: 1873-3468
Titre abrégé: FEBS Lett
Pays: England
ID NLM: 0155157

Informations de publication

Date de publication:
12 2021
Historique:
revised: 05 11 2021
received: 21 05 2021
accepted: 06 11 2021
pubmed: 16 11 2021
medline: 12 1 2022
entrez: 15 11 2021
Statut: ppublish

Résumé

Interleukin-6 (IL-6) and interleukin-11 (IL-11) are two important pleiotropic cytokines, both of which signal through a homodimer of the β-receptor gp130. Specificity is gained through the unique, nonsignaling α-receptors IL-6R and IL-11R. Soluble variants of IL-6R and IL-11R also exist. Both membrane-bound receptors can be cleaved by the metalloprotease ADAM10. Here, we use ten different chimeric receptors consisting of different parts of IL-6R and IL-11R and analyze their susceptibility toward cleavage by ADAM10. As expected, all chimeras are substrates of ADAM10. However, we observed that cleavage of chimeric receptors containing the stalk region of the IL-11R could be blocked by the protease inhibitor GI (selective for ADAM10), but not by the protease inhibitor GW (selective for both ADAM10 and ADAM17), suggesting that another protease besides ADAM10 is involved in cleavage of these chimeras.

Identifiants

pubmed: 34778975
doi: 10.1002/1873-3468.14230
doi:

Substances chimiques

Interleukin-6 0
Protease Inhibitors 0
Receptors, Interleukin-11 0
Recombinant Fusion Proteins 0
Ionomycin 56092-81-0
ADAM10 Protein EC 3.4.24.81

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

3072-3082

Informations de copyright

© 2021 The Authors. FEBS Letters published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.

Références

Garbers C, Hermanns H, Schaper F, Müller-Newen G, Grötzinger J, Rose-John S and Scheller J (2012) Plasticity and cross-talk of interleukin 6-type cytokines. Cytokine Growth Factor Rev 23, 85-97.
Garbers C, Heink S, Korn T and Rose-John S (2018) Interleukin-6: designing specific therapeutics for a complex cytokine. Nat Rev Drug Discov 17, 395-412.
Jones SA and Jenkins BJ (2018) Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol 18, 773-789.
Tay MZ, Poh CM, Renia L, MacAry PA and Ng LFP (2020) The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol 20, 363-374.
Xu X, Han M, Li T, Sun W, Wang D, Fu B, Zhou Y, Zheng X, Yang Y, Li X et al. (2020) Effective treatment of severe COVID-19 patients with tocilizumab. Proc Natl Acad Sci USA 117, 10970-10975.
Guaraldi G, Meschiari M, Cozzi-Lepri A, Milic J, Tonelli R, Menozzi M, Franceschini E, Cuomo G, Orlando G, Borghi V et al. (2020) Tocilizumab in patients with severe COVID-19: a retrospective cohort study. Lancet Rheumatol 2, e474-e484.
Wilde MI and Faulds D (1998) Oprelvekin: a review of its pharmacology and therapeutic potential in chemotherapy-induced thrombocytopenia. BioDrugs 10, 159-171.
Putoczki T, Thiem S, Loving A, Busuttil R, Wilson N, Ziegler P, Nguyen P, Preaudet A, Farid R, Edwards K et al. (2013) Interleukin-11 Is the dominant IL-6 family cytokine during gastrointestinal tumorigenesis and can be targeted therapeutically. Cancer Cell 24, 257-271.
Ernst M, Najdovska M, Grail D, Lundgren-May T, Buchert M, Tye H, Matthews V, Armes J, Bhathal P, Hughes N et al. (2008) STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J Clin Investig 118, 1727-1738.
Balic JJ, Garbers C, Rose-John S, Yu L and Jenkins BJ (2017) Interleukin-11-driven gastric tumourigenesis is independent of trans-signalling. Cytokine 92, 118-123.
Winship AL, Van Sinderen M, Donoghue J, Rainczuk K and Dimitriadis E (2016) Targeting interleukin-11 receptor-α impairs human endometrial cancer cell proliferation and invasion in vitro and reduces tumour growth and metastasis in vivo. Mol Cancer Ther 15, 720-730.
Lokau J and Garbers C (2020) Biological functions and therapeutic opportunities of soluble cytokine receptors. Cytokine Growth Factor Rev 55, 94-108.
Lust J, Donovan K, Kline M, Greipp P, Kyle R and Maihle N (1992) Isolation of an mRNA encoding a soluble form of the human interleukin-6 receptor. Cytokine 4, 96-100.
Müllberg J, Schooltink H, Stoyan T, Günther M, Graeve L, Buse G, Mackiewicz A, Heinrich P and Rose-John S (1993) The soluble interleukin-6 receptor is generated by shedding. Eur J Immunol 23, 473-480.
Matthews V, Schuster B, Schutze S, Bussmeyer I, Ludwig A, Hundhausen C, Sadowski T, Saftig P, Hartmann D, Kallen KJ et al. (2003) Cellular cholesterol depletion triggers shedding of the human interleukin-6 receptor by ADAM10 and ADAM17 (TACE). J Biol Chem 278, 38829-38839.
Garbers C, Jänner N, Chalaris A, Moss ML, Floss DM, Meyer D, Koch-Nolte F, Rose-John S and Scheller J (2011) Species specificity of ADAM10 and ADAM17 proteins in interleukin-6 (IL-6) trans-signaling and novel role of ADAM10 in inducible IL-6 receptor shedding. J Biol Chem 286, 14804-14811.
Baran P, Nitz R, Grötzinger J, Scheller J and Garbers C (2013) Minimal interleukin (IL-)6 receptor stalk composition for IL-6R shedding and IL-6 classic signaling. J Biol Chem 288, 14756-14768.
Riethmueller S, Ehlers JC, Lokau J, Düsterhöft S, Knittler K, Dombrowsky G, Grötzinger J, Rabe B, Rose-John S and Garbers C (2016) Cleavage site localization differentially controls interleukin-6 receptor proteolysis by ADAM10 and ADAM17. Sci Rep 6, 25550.
Riethmueller S, Somasundaram P, Ehlers JC, Hung C-WW, Flynn CM, Lokau J, Agthe M, Düsterhöft S, Zhu Y, Grötzinger J et al. (2017) Proteolytic origin of the soluble human IL-6R in vivo and a decisive role of N-glycosylation. PLoS Biol 15, e2000080.
Horiuchi S, Koyanagi Y, Zhou Y, Miyamoto H, Tanaka Y, Waki M, Matsumoto A, Yamamoto M and Yamamoto N (1994) Soluble interleukin-6 receptors released from T cell or granulocyte/macrophage cell lines and human peripheral blood mononuclear cells are generated through an alternative splicing mechanism. Eur J Immunol 24, 1945-1948.
Lokau J, Nitz R, Agthe M, Monhasery N, Aparicio-Siegmund S, Schumacher N, Wolf J, Möller-Hackbarth K, Waetzig GH, Grötzinger J et al. (2016) Proteolytic cleavage governs interleukin-11 trans-signaling. Cell Rep 14, 1761-1773.
Sun BB, Maranville JC, Peters JE, Stacey D, Staley JR, Blackshaw J, Burgess S, Jiang T, Paige E, Surendran P et al. (2018) Genomic atlas of the human plasma proteome. Nature 558, 73-79.
Monhasery N, Moll J, Cuman C, Franke M, Lamertz L, Nitz R, Gorg B, Häussinger D, Lokau J, Floss DM et al. (2016) Transcytosis of IL-11 and apical redirection of gp130 is mediated by IL-11alpha receptor. Cell Rep 16, 1067-1081.
Nitz R, Lokau J, Aparicio-Siegmund S, Scheller J and Garbers C (2015) Modular organization of interleukin-6 and interleukin-11 α-receptors. Biochimie 119, 175-182.
Ludwig A, Hundhausen C, Lambert M, Broadway N, Andrews R, Bickett D, Leesnitzer M and Becherer J (2005) Metalloproteinase inhibitors for the disintegrin-like metalloproteinases ADAM10 and ADAM17 that differentially block constitutive and phorbol ester-inducible shedding of cell surface molecules. Comb Chem High Throughput Screen 8, 161-171.
Hundhausen C, Misztela D, Berkhout T, Broadway N, Saftig P, Reiss K, Hartmann D, Fahrenholz F, Postina R, Matthews V et al. (2003) The disintegrin-like metalloproteinase ADAM10 is involved in constitutive cleavage of CX3CL1 (fractalkine) and regulates CX3CL1-mediated cell-cell adhesion. Blood 102, 1186-1195.
Lokau J, Agthe M, Flynn CM and Garbers C (2017) Proteolytic control of Interleukin-11 and Interleukin-6 biology. Biochim Biophys Acta 1864, 2105-2117.
Lokau J, Agthe M and Garbers C (2016) Generation of soluble interleukin-11 and interleukin-6 receptors: a crucial function for proteases during inflammation. Mediators Inflamm 2016, 1785021.
Murai T, Maruyama Y, Mio K, Nishiyama H, Suga M and Sato C (2011) Low cholesterol triggers membrane microdomain-dependent CD44 shedding and suppresses tumor cell migration. J Biol Chem 286, 1999-2007.
Kojro E, Gimpl G, Lammich S, Marz W and Fahrenholz F (2001) Low cholesterol stimulates the nonamyloidogenic pathway by its effect on the alpha -secretase ADAM 10. Proc Natl Acad Sci USA 98, 5815-5820.
Le Gall S, Bobé P, Reiss K, Horiuchi K, Niu X-D, Lundell D, Gibb D, Conrad D, Saftig P and Blobel C (2009) ADAMs 10 and 17 represent differentially regulated components of a general shedding machinery for membrane proteins such as transforming growth factor alpha, L-selectin, and Tumor Necrosis Factor Alpha. Mol Biol Cell 20, 1785-1794.

Auteurs

Juliane Lokau (J)

Department of Pathology, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany.

Christoph Garbers (C)

Department of Pathology, Medical Faculty, Otto-von-Guericke-University, Magdeburg, Germany.

Articles similaires

[Redispensing of expensive oral anticancer medicines: a practical application].

Lisanne N van Merendonk, Kübra Akgöl, Bastiaan Nuijen
1.00
Humans Antineoplastic Agents Administration, Oral Drug Costs Counterfeit Drugs

Smoking Cessation and Incident Cardiovascular Disease.

Jun Hwan Cho, Seung Yong Shin, Hoseob Kim et al.
1.00
Humans Male Smoking Cessation Cardiovascular Diseases Female
Humans United States Aged Cross-Sectional Studies Medicare Part C
1.00
Humans Yoga Low Back Pain Female Male

Classifications MeSH