Distinct Roles of Sphingosine Kinase 1 and 2 in Murine Collagen-Induced Arthritis1 (original) (raw)
Journal Article
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore
,
Singapore
Search for other works by this author on:
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore
,
Singapore
Search for other works by this author on:
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore
,
Singapore
Search for other works by this author on:
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore
,
Singapore
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
, Glasgow,
United Kingdom
Search for other works by this author on:
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
, Glasgow,
United Kingdom
Search for other works by this author on:
Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore
,
Singapore
Division of Immunology, Infection and Inflammation, Glasgow Biomedical Research Centre, University of Glasgow
, Glasgow,
United Kingdom
Address correspondence and reprint requests to Dr. Bernard P. Leung, Department of Physiology, 2 Medical Drive, MD9, National University of Singapore, Singapore. E-mail address: [email protected]
Search for other works by this author on:
Received:
31 December 2008
Published:
01 August 2009
Cite
Wen-Qi Lai, Anastasia Windy Irwan, Hong Heng Goh, Alirio J Melendez, Iain B McInnes, Bernard P Leung, Distinct Roles of Sphingosine Kinase 1 and 2 in Murine Collagen-Induced Arthritis, The Journal of Immunology, Volume 183, Issue 3, August 2009, Pages 2097–2103, https://doi.org/10.4049/jimmunol.0804376
Close
Navbar Search Filter Mobile Enter search term Search
Abstract
Sphingosine kinase (SphK) phosphorylates sphingosine into sphingosine-1-phosphate (S1P). S1P plays a critical role in angiogenesis, inflammation, and various pathologic conditions. To date, two mammalian isoenzymes, SphK1 and SphK2, have been identified. Although both SphK1 and SphK2 share overall homology and produce the common product, S1P, it has been proposed they display different unique and separate functions. In this study, we examined the role of SphK1 and SphK2 in a murine collagen-induced arthritis model by down-regulating each isoenzyme via specific small interfering RNA (siRNA). Prophylactic i.p. administration of SphK1 siRNA significantly reduced the incidence, disease severity, and articular inflammation compared with control siRNA recipients. Treatment of SphK1 siRNA also down-regulated serum levels of S1P, IL-6, TNF-α, IFN-γ, and IgG2a anti-collagen Ab. Ex vivo analysis demonstrated significant suppression of collagen-specific proinflammatory/Th1 cytokine (IL-6, TNF-α, IFN-γ) release in SphK siRNA-treated mice. Interestingly, mice received with SphK2 siRNA develop more aggressive disease; higher serum levels of IL-6, TNF-α, and IFN-γ; and proinflammatory cytokine production to collagen in vitro when compared with control siRNA recipients. Together, these results demonstrate the distinct immunomodulatory roles of SphK1 and SphK2 in the development of inflammatory arthritis by regulating the release of proinflammatory cytokines and T cell responses. These findings raise the possibility that drugs which specifically target SphK1 activity may play a beneficial role in the treatment of inflammatory arthritis.
Copyright © 2009 by The American Association of Immunologists, Inc.
You do not currently have access to this article.
Personal account
- Sign in with email/username & password
- Get email alerts
- Save searches
- Purchase content
- Activate your purchase/trial code
- Add your ORCID iD
Get help with access
Institutional access
Access to content on Oxford Academic is often provided through institutional subscriptions and purchases. If you are a member of an institution with an active account, you may be able to access content in one of the following ways:
IP based access
Typically, access is provided across an institutional network to a range of IP addresses. This authentication occurs automatically, and it is not possible to sign out of an IP authenticated account.
Sign in through your institution
Choose this option to get remote access when outside your institution. Shibboleth/Open Athens technology is used to provide single sign-on between your institution's website and Oxford Academic.
- Click Sign in through your institution.
- Select your institution from the list provided, which will take you to your institution's website to sign in.
- When on the institution site, please use the credentials provided by your institution. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If your institution is not listed or you cannot sign in to your institution's website, please contact your librarian or administrator.
Sign in with a library card
Enter your library card number to sign in. If you cannot sign in, please contact your librarian.
Society Members
Society member access to a journal is achieved in one of the following ways:
Sign in through society site
Many societies offer single sign-on between the society website and Oxford Academic. If you see "Sign in through society site" in the sign in pane within a journal:
- Click Sign in through society site.
- When on the society site, please use the credentials provided by that society. Do not use an Oxford Academic personal account.
- Following successful sign in, you will be returned to Oxford Academic.
If you do not have a society account or have forgotten your username or password, please contact your society.
Sign in using a personal account
Some societies use Oxford Academic personal accounts to provide access to their members. See below.
Personal account
A personal account can be used to get email alerts, save searches, purchase content, and activate subscriptions.
Some societies use Oxford Academic personal accounts to provide access to their members.
Viewing your signed in accounts
Click the account icon in the top right to:
- View your signed in personal account and access account management features.
- View the institutional accounts that are providing access.
Signed in but can't access content
Oxford Academic is home to a wide variety of products. The institutional subscription may not cover the content that you are trying to access. If you believe you should have access to that content, please contact your librarian.
Institutional account management
For librarians and administrators, your personal account also provides access to institutional account management. Here you will find options to view and activate subscriptions, manage institutional settings and access options, access usage statistics, and more.
Purchase
Short-term Access
To purchase short-term access, please sign in to your personal account above.
Don't already have a personal account? Register
Distinct Roles of Sphingosine Kinase 1 and 2 in Murine Collagen-Induced Arthritis1 - 24 Hours access
EUR €34.00
GBP £28.00
USD $38.00
Rental
This article is also available for rental through DeepDyve.