TPL2 Is a Key Regulator of Intestinal Inflammation in Clostridium difficile Infection

Infection and Immunity
Yuanguo WangXingmin Sun

Abstract

Tumor progression locus 2 (TPL2), a serine/threonine protein kinase, is a major inflammatory mediator in immune cells. The predominant inflammatory actions of TPL2 depend on the activation of mitogen-activated protein kinases (MAPK) and the upregulated production of the cytokines tumor necrosis factor alpha (TNF-α) and interleukin 1β (IL-1β) in macrophages and dendritic cells in response to lipopolysaccharide (LPS). Significant increases in TNF-α, IL-6, IL-β, and IL-8 levels in patients with Clostridium difficile infection (CDI) have been reported. Both TNF-α and IL-6 have been postulated to play key roles in the systemic inflammatory response in CDI, and IL-8 is essential for the development of local intestinal inflammatory responses in CDI. The objective of this study was to elucidate the role of TPL2 in the pathogenesis of CDI. We found that TPL2 was significantly activated in human and mouse intestinal tissues upon C. difficile toxin exposure or CDI. We further demonstrated that TPL2 knockout (TPL2-KO) mice were significantly more resistant to CDI than wild-type mice, with significantly reduced production of TNF-α, IL-6, IL-1β, KC (a mouse homologue of IL-8), and myeloperoxidase (MPO) in the ceca and colons of TPL2-KO mice....Continue Reading

References

Feb 1, 1994·Proceedings of the National Academy of Sciences of the United States of America·C PothoulakisS E Leeman
Mar 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·C PatriotisP N Tsichlis
Jan 27, 1994·The New England Journal of Medicine·C P KellyJ T LaMont
Sep 28, 1999·Molecular Medicine Today·E Herlaar, Z Brown
May 26, 2004·Proceedings of the National Academy of Sciences of the United States of America·Pauline M AntonCharalabos Pothoulakis
Sep 17, 2004·The Journal of Clinical Investigation·Kenji SugimotoTetsuya Matsuguchi
Jan 28, 2005·Journal of Medical Microbiology·Séverine PéchinéAnne Collignon
Apr 12, 2005·Nature Reviews. Microbiology·Klaus Aktories, Joseph T Barbieri
Apr 16, 2005·Clinical Microbiology Reviews·Daniel E Voth, Jimmy D Ballard
Feb 18, 2006·Proceedings of the National Academy of Sciences of the United States of America·Ashish BanerjeeSteve Gerondakis
Jul 20, 2007·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Jin Young LeeJung Mogg Kim
Jul 21, 2007·Internal Medicine Journal·B ElliottT V Riley
Oct 14, 2008·Gastroenterology·Xinhua ChenCiarán P Kelly
Dec 11, 2008·Journal of Visualized Experiments : JoVE·Melanie P MatheuIan Parker
Aug 12, 2009·The Journal of Experimental Medicine·Frank KaiserAnne O'Garra
Nov 26, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lisa A MielkeWendy T Watford
Jan 22, 2010·Journal of Dental Research·T OhnishiT Matsuguchi
Jan 1, 2008·CSH Protocols·Joachim Weischenfeldt, Bo Porse
Mar 8, 2011·Cancer Letters·Maria VougioukalakiAristides G Eliopoulos
Mar 18, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Mizuho HasegawaNaohiro Inohara
May 18, 2011·Infection and Immunity·Xingmin SunHanping Feng
Jul 1, 2010·Toxins·Xingmin SunHanping Feng
Mar 14, 2012·FEMS Immunology and Medical Microbiology·Prerna Vohra, Ian R Poxton
Jun 13, 2012·Infection and Immunity·Irene JarchumEric G Pamer
Oct 16, 2012·The Journal of Clinical Investigation·Vasiliki KoliarakiGeorge Kollias
Dec 25, 2012·Infection and Immunity·Linda D BoboDavid B Haslam
Jul 12, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Finlay W McNabAnne O'Garra
Feb 18, 2014·The International Journal of Biochemistry & Cell Biology·Guy Martel, Simon Rousseau
Jul 28, 2016·Infection and Immunity·Nicole M ChumblerD Borden Lacy
Aug 31, 2016·Nature Reviews. Microbiology·Michael C AbtEric G Pamer

❮ Previous
Next ❯

Citations

Jan 11, 2020·Artificial Cells, Nanomedicine, and Biotechnology·Ying LiYijian Chen
Aug 21, 2021·Therapeutic Advances in Gastroenterology·Katia FettucciariGabrio Bassotti

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.