NDLI: Phospholipase C activator m-3M3FBS protects against morbidity and mortality associated with sepsis.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Lee, Sung Kyun Shim, Jae Woong Baek, Suk-Hwan Zabel, Brian A. Kim, Sang Doo Jung, Young Su Park, Joon Seong Kwon, Soonil Lee, Ha Young Bae, Yoe-Sik Kim, Hak Jung
Description	Country affiliation: South Korea Author Affiliation: Kim SD ( Department of Biological Sciences, Sungkyunkwan University, Suwon 440-746, South Korea.)
Abstract	Although phospholipase C (PLC) is a crucial enzyme required for effective signal transduction and leukocyte activation, the role of PLC in polymicrobial sepsis remains unclear. In this study, we show that the direct PLC activator m-3M3FBS treatment significantly attenuates vital organ inflammation, widespread immune cell apoptosis, and mortality in a mouse sepsis model induced by lethal cecal ligation and puncture challenge. Mechanistically, m-3M3FBS-dependent protection was largely abolished by pretreatment of mice with the PLC-selective inhibitor U-73122, thus confirming PLC agonism by m-3M3FBS in vivo. PLC activation enhanced the bactericidal activity and hydrogen peroxide production of mouse neutrophils, and it also enhanced the production of IFN-Î³ and IL-12 while inhibiting proseptic TNF- and IL-1ß production in cecal ligation and puncture mice. In a second model of sepsis, PLC activation also inhibited the production of TNF- and IL-1ß following systemic LPS challenge. In conclusion, we show that agonizing the central signal transducing enzyme PLC by m-3M3FBS can reverse the progression of toxic shock by triggering multiple protective downstream signaling pathways to maintain organ function, leukocyte survival, and to enhance microbial killing.
ISSN	00221767
e-ISSN	15506606
Journal	The Journal of Immunology
Issue Number	4
Volume Number	189
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2012-08-15
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Sepsis Drug Therapy Metabolism Sulfonamides Pharmacology Type C Phospholipases Animals Apoptosis Drug Effects Cytokines Biosynthesis Disease Models, Animal Enzyme Activation Physiology Immunohistochemistry In Situ Nick-end Labeling Mice Mice, Inbred Icr Neutrophils Immunology Mortality Research Support, Non-u.s. Gov't Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in