Gedunin Binds to Myeloid Differentiation Protein 2 and Impairs Lipopolysaccharide-Induced Toll-Like Receptor 4 Signaling in Macrophages

Molecular Pharmacology
Perla Villani BorgesCarmen Penido

Abstract

Recognition of bacterial lipopolysaccharide (LPS) by innate immune system is mediated by the cluster of differentiation 14/Toll-like receptor 4/myeloid differentiation protein 2 (MD-2) complex. In this study, we investigated the modulatory effect of gedunin, a limonoid from species of the Meliaceae family described as a heat shock protein Hsp90 inhibitor, on LPS-induced response in immortalized murine macrophages. The pretreatment of wild-type (WT) macrophages with gedunin (0.01-100 µM, noncytotoxic concentrations) inhibited LPS (50 ng/ml)-induced calcium influx, tumor necrosis factor-α, and nitric oxide production in a concentration-dependent manner. The selective effect of gedunin on MyD88-adapter-like/myeloid differentiation primary response 88- and TRIF-related adaptor molecule/TIR domain-containing adapter-inducing interferon-β-dependent signaling pathways was further investigated. The pretreatment of WT, TIR domain-containing adapter-inducing interferon-β knockout, and MyD88 adapter-like knockout macrophages with gedunin (10 µM) significantly inhibited LPS (50 ng/ml)-induced tumor necrosis factor-α and interleukin-6 production, at 6 hours and 24 hours, suggesting that gedunin modulates a common event between both signalin...Continue Reading

References

Oct 15, 1984·Journal of Molecular Biology·D EisenbergR Wall
Jan 1, 1995·Annual Review of Immunology·R J Ulevitch, P S Tobias
Oct 1, 1995·American Journal of Respiratory Cell and Molecular Biology·S L CamhiA M Choi
Mar 17, 1995·Biochemical and Biophysical Research Communications·S Arias-NegreteK Chadee
Jan 1, 1993·Annual Review of Immunology·K W MooreT R Mosmann
May 13, 1999·Proceedings of the National Academy of Sciences of the United States of America·C A ByrdA Ding
Jun 8, 1999·The Journal of Experimental Medicine·R ShimazuM Kimoto
May 16, 2000·The Journal of Biological Chemistry·A J WeaverD O Toft
Jul 6, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·M HirschfeldJ J Weis
Sep 28, 2000·Journal of Applied Physiology·C C Dos Santos, A S Slutsky
Dec 21, 2000·American Journal of Physiology. Heart and Circulatory Physiology·A A Knowlton, L Sun
Jul 27, 2001·American Journal of Respiratory Cell and Molecular Biology·V MalhotraH R Wong
Jul 27, 2001·Journal of Cellular Physiology·K Richter, J Buchner
Aug 14, 2001·European Journal of Immunology·C A Byrd-LeiferA Ding
Mar 5, 2002·Nature Medicine·Tzong-Shyuan Lee, Lee-Young Chau
Jul 18, 2002·American Journal of Physiology. Gastrointestinal and Liver Physiology·Grace L Su
Sep 18, 2002·The EMBO Journal·Aristides G EliopoulosPhilip N Tsichlis
Dec 12, 2002·Cellular and Molecular Life Sciences : CMLS·D Picard
Feb 18, 2003·Molecular Biology of the Cell·Virginia L Vega, Antonio De Maio
Jun 21, 2003·The Journal of Immunology : Official Journal of the American Association of Immunologists·Johannes G BodeDieter Häussinger
Jul 12, 2003·The Journal of Biological Chemistry·Masako Yoshida, Yong Xia
Aug 15, 2003·World Journal of Gastroenterology : WJG·Yong SongXian-Zhong Meng
Sep 10, 2003·Journal of Leukocyte Biology·B BeutlerR J Ulevitch
Oct 1, 2003·The Journal of Experimental Medicine·Katherine A FitzgeraldDouglas T Golenbock
Mar 3, 2004·Molecular Interventions·Fulvio D'AcquistoSankar Ghosh
Jun 25, 2004·Nucleic Acids Research·Todd J DolinskyNathan A Baker
Jul 2, 2004·Nature Reviews. Immunology·Shizuo Akira, Kiyoshi Takeda
Sep 1, 2005·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·C PenidoM G M O Henriques
Sep 24, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stuart A RushworthMaria A O'Connell
Dec 8, 2005·Biochemistry and Cell Biology = Biochimie Et Biologie Cellulaire·Rongmin Zhao, Walid A Houry

❮ Previous
Next ❯

Citations

Apr 23, 2016·International Journal of Molecular Sciences·Kiyofumi NinomiyaToshio Morikawa
Sep 20, 2016·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Perla Villani BorgesCarmen Penido
Nov 20, 2016·Journal of Cellular and Molecular Medicine·Yali ZhangGuang Liang
Jan 26, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Teresa M BragaAgostinho Cruz
Aug 8, 2021·International Journal of Molecular Sciences·Su Young JungSeung Geun Yeo

❮ Previous
Next ❯

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.