Host Defense Peptide LL-37-Mediated Chemoattractant Properties, but Not Anti-Inflammatory Cytokine IL-1RA Production, Is Selectively Controlled by Cdc42 Rho GTPase via G Protein-Coupled Receptors and JNK Mitogen-Activated Protein Kinase

Frontiers in Immunology
Mahadevappa HemshekharNeeloffer Mookherjee

Abstract

The human host defense peptide LL-37 promotes immune activation such as induction of chemokine production and recruitment of leukocytes. Conversely, LL-37 also mediates anti-inflammatory responses such as production of anti-inflammatory cytokines, e.g., IL-1RA, and the control of pro-inflammatory cytokines, e.g., TNF. The mechanisms regulating these disparate immunomodulatory functions of LL-37 are not completely understood. Rho GTPases are GTP-binding proteins that promote fundamental immune functions such as chemokine production and recruitment of leukocytes. However, recent studies have shown that distinct Rho proteins can both negatively and positively regulate inflammation. Therefore, we interrogated the role of Rho GTPases in LL-37-mediated immunomodulation. We demonstrate that LL-37-induced production of chemokines, e.g., GRO-α and IL-8 is largely dependent on Cdc42/Rac1 Rho GTPase, but independent of the Ras pathway. In contrast, LL-37-induced production of the anti-inflammatory cytokine IL-1RA is not dependent on either Cdc42/Rac1 RhoGTPase or Ras GTPase. Functional studies confirmed that LL-37-induced recruitment of leukocytes (monocytes and neutrophils) is also dependent on Cdc42/Rac1 RhoGTPase activity. We demonstra...Continue Reading

References

Jan 16, 2002·International Immunopharmacology·Yingying LeJi Ming Wang
Sep 24, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Monisha G ScottRobert E W Hancock
Oct 11, 2002·The New England Journal of Medicine·Peck Y OngDonald Y M Leung
Oct 11, 2002·The Journal of Pathology·Friedrich PaulsenWolf Petersen
Feb 14, 2003·American Journal of Physiology. Cell Physiology·Dezheng ZhaoCharalabos Pothoulakis
Mar 22, 2003·Proceedings of the National Academy of Sciences of the United States of America·M A LokutaA Huttenlocher
Jan 7, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Donald J DavidsonDavid P Speert
Mar 9, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dawn M E BowdishRobert E W Hancock
Mar 8, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Galina V ShurinMichael R Shurin
Feb 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Neeloffer MookherjeeRobert E W Hancock
Oct 13, 2006·Molecular Biology and Evolution·Anthony BoureuxPhilippe Fort
Feb 21, 2007·Cellular and Molecular Life Sciences : CMLS·N Mookherjee, R E W Hancock
Nov 21, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Jie YuRobert E W Hancock
Jun 5, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yang HuLionel B Ivashkiv
Apr 22, 2009·Molecular BioSystems·Neeloffer MookherjeeRobert E W Hancock
Jul 17, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Neeloffer MookherjeeRobert E W Hancock
Sep 15, 2009·Cell Host & Microbe·Jae-Min YukEun-Kyeong Jo
Oct 8, 2009·Journal of Leukocyte Biology·Mona DossKevan L Hartshorn
Jul 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Anne M van der DoesPeter H Nibbering
Sep 3, 2010·Methods in Molecular Biology·Mario ChiarielloJ Silvio Gutkind
Mar 29, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Kelly L BrownPauline Johnson
May 12, 2012·Annals of Dermatology·Markus ReinholzJürgen Schauber
Jun 16, 2012·Frontiers in Immunology·Ka-Yee Grace Choi, Neeloffer Mookherjee
Jun 29, 2012·Journal of Innate Immunity·Ka-Yee ChoiNeeloffer Mookherjee
Dec 19, 2012·Cellular Immunology·Dieter VandammeLiliane Schoofs
Feb 5, 2013·Methods in Enzymology·Chunmin Dong, Guangyu Wu
Feb 5, 2013·International Immunopharmacology·Yang RuanTieying Sun
Aug 8, 2013·Journal of Cardiovascular Pharmacology·Yuyan LuYawei Xu
Sep 14, 2013·Journal of the Peripheral Nervous System : JPNS·Kelly A LangertEvan B Stubbs
Nov 5, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·J Michelle Kahlenberg, Mariana J Kaplan
Feb 28, 2014·British Journal of Pharmacology·Maté BiroWolfgang Weninger

❮ Previous
Next ❯

Citations

May 17, 2019·Journal of Periodontal Research·Alexandra AidoukovitchBengt-Olof Nilsson
Sep 12, 2020·Advanced Materials·Saber Amin YavariMichiel Croes
Sep 26, 2020·Frontiers in Immunology·Mahadevappa HemshekharNeeloffer Mookherjee
Feb 29, 2020·Nature Reviews. Drug Discovery·Neeloffer MookherjeeDonald J Davidson
Oct 30, 2020·Cells·Nina D AnfinogenovaDmitriy N Atochin
Mar 19, 2021·ACS Infectious Diseases·Carly DeusenberyAnita Shukla
Jul 3, 2021·Biomolecules·Marija PetkovicHåvard Jenssen
Aug 10, 2021·Frontiers in Immunology·Jinyang CaiYan Cao
Aug 28, 2021·International Journal of Molecular Sciences·Ga-Hyun SonKeun-Young Lee
Sep 17, 2021·Archivum Immunologiae Et Therapiae Experimentalis·Bruno Rivas-SantiagoAdrian Rodriguez-Carlos

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPases
nucleotide exchange
GTPase
PMA
ELISA
PCR

Software Mentioned

PathScan

Related Concepts

Related Feeds

Anti-inflammatory Treatments

A drug or substance that reduces inflammation (redness, swelling, and pain) in the body. Anti-inflammatory agents block certain substances in the body that cause inflammation and swelling. Discover the latest research on anti-inflammatory treatments here