Functional analysis of PRSS33, a eosinophil-specific protease

• Project/Area Number: 15K09560
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Collagenous pathology/Allergology
• Research Institution: National Center for Child Health and Development
• Principal Investigator: Matsumoro Kenji 国立研究開発法人国立成育医療研究センター, 免疫アレルギー・感染研究部, 部長 (60181765)
• Co-Investigator(Renkei-kenkyūsha): Toyama Sumika 国立成育医療研究センター研究所, 免疫アレルギー・感染研究部 (50805893)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2016: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2015: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
• Keywords: 好酸球 / プロテアーゼ / PRSS33 / リモデリング / 組織リモデリング

Outline of Final Research Achievements

We investigated the function of an eosinophil-specific proteases/proteinase protease serine 33 (PRSS33), in vitro and in vivo. GM-CSF-activated human eosinophils but not resting eosinophils were stained with anti-PRSS33 mAb, suggesting that PRSS33 is specifically expressed on the granular membrane of eosinophils. However, PRSS33 was not secreted to the supernatant even after stimulation with secretagogues. Recombinant PRSS33 protein (rPRSS33) created with a baculovirus system induced significant expression of collagen and fibronectin mRNAs in human fibroblasts at least in part via protease-activated receptor-2 activation. PRSS33 knockout mouse created by CRISPR/Cas9 system was employed to papain-inhalation model and long term-house dust mite-inhalation model, however, no significant effects were observed.

Research Products

• [Journal Article] Human eosinophils constitutively express a unique serine protease, PRSS33 (2017)
  • Author(s): Toyama S, Okada N, Matsuda A, Morita H, Saito H, Fujisawa T, Nakae S, Karasuyama H, Matsumoto K.
  • Journal Title: Allergology International Volume: 66 Issue: 3 Pages: 463-471
  • DOI: 10.1016/j.alit.2017.01.001
  • NAID: 130005858869
  • ISSN: 1323-8930, 1440-1592
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Platelets constitutively express IL-33 protein and modulate eosinophilic airway inflammation. (2016)
  • Author(s): Takeda T, Unno H, Morita H, Futamura K, Emi-Sugie M, Arae K, Shoda T, Okada N, Igarashi A, Inoue E, Kitazawa H, Nakae S, Saito H, Matsumoto K, Matsuda A.
  • Journal Title: J Allergy Clin Immunol Volume: In Press Issue: 5 Pages: 1395-1403
  • DOI: 10.1016/j.jaci.2016.01.032
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] An Interleukin-33-Mast Cell-Interleukin-2 Axis Suppresses Papain-Induced Allergic Inflammation by Promoting Regulatory T Cell Numbers. (2015)
  • Author(s): Morita H, Arae K, Unno H, Miyauchi K, Toyama S, Nambu A, Oboki K, Ohno T, Motomura K, Matsuda A, Yamaguchi S, Narushima S, Kajiwara N, Iikura M, Suto H, McKenzie AN, Takahashi T, Karasuyama H, Okumura K, Azuma M, Moro K, Akdis CA, Galli SJ, Koyasu S, Kubo M, Sudo K, Saito H, Matsumoto K, Nakae S.
  • Journal Title: Immunity Volume: 43 Issue: 1 Pages: 175-86
  • DOI: 10.1016/j.immuni.2015.06.021
  • NAID: 40020962854
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Presentation] A novel protease, PRSS33 (serine protease 33, EOS), is specifically and constitutively expressed in human eosinophils (2015)
  • Author(s): Sumika Toyama, Akio Matsuda, Hajime Karasuyama, Hirohisa Saito, Susumu Nakae, Kenji Matsumoto
  • Organizer: 9th Biennial Symposium of International Eosinophil Society
  • Place of Presentation: Chicago, IL
  • Year and Date: 2015-07-14
  • Int'l Joint Research