Login to MyKarger

New to MyKarger? Click here to sign up.

Login with Facebook

Forgot Password? Reset your password

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login (Shibboleth)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Table of Contents
Vol. 1, No. 6, 2009
Issue release date: October 2009
Section title: Research Article
Free Access
J Innate Immun 2009;1:607–617

Calcium-Independent Phospholipase A2β Is Dispensable in Inflammasome Activation and Its Inhibition by Bromoenol Lactone

Franchi L.a · Chen G.a · Marina-Garcia N.a · Abe A.b · Qu Y.c · Bao S.d · Shayman J.A.b · Turk J.d · Dubyak G.R.c · Núñez G.a
aDepartment of Pathology and Comprehensive Cancer Center, and bDepartment of Internal Medicine, University of Michigan Medical School, Ann Arbor, Mich., cDepartment of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, Ohio, and dDepartment of Medicine, Division of Endocrinology, Metabolism, and Lipid Research, Washington University School of Medicine, St. Louis, Mo., USA
email Corresponding Author

Dr. Gabriel Núñez

Department of Pathology and Comprehensive Cancer Center

University of Michigan Medical School

1500 E. Medical Center Drive, Ann Arbor, MI 48109 (USA)

Tel. +1 734 764 8514, Fax +1 734 647 9654, E-Mail bclx@umich.edu

Do you have an account?

Login Information

Contact Information

I have read the Karger Terms and Conditions and agree.


Calcium-independent phospholipase A2 (iPLA2) has been suggested to play an important role in the activation of caspase-1 induced by lipopolysaccharides (LPS). Here, we used pharmacological and genetic approaches to study the role of iPLA2 in the activation of caspase-1. Bromoenol lactone (BEL), an inhibitor that was originally used to support a role for iPLA2 in the secretion of IL-1β, prevented caspase-1 activation induced by LPS and ATP as described, and also activation triggered by Salmonella infection and cytosolic flagellin, which rely on the Nlrc4 inflammasome. Analysis of BEL enantiomers showed that the S-BEL form was more effective than R-BEL in inhibiting the inflammasome, suggesting a role for iPLA2β. However, caspase-1 activation and IL-1β secretion and their inhibition by BEL were unimpaired in macrophages deficient in iPLA2β. BEL was originally identified as an inhibitor of serine proteases. Consistent with the latter, the serine proteases inhibitors TPCK, TLCK and AAF-cmk prevented the activation of the Nlrc4 and Nlrp3 inflammasomes while pan-cathepsin inhibitors were ineffective. These results indicate that iPLA2β is not critical for caspase-1 activation as currently proposed. Instead, the results suggest that serine protease(s) targeted by BEL may play a critical role in the activation of the inflammasome triggered by microbial stimuli.

© 2009 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: March 24, 2009
Accepted: April 30, 2009
Published online: July 01, 2009
Issue release date: October 2009

Number of Print Pages: 11
Number of Figures: 7
Number of Tables: 0

ISSN: 1662-811X (Print)
eISSN: 1662-8128 (Online)

For additional information: http://www.karger.com/JIN

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.