| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
* Department of Microbiology, University of British Columbia, and
British Columbia Research Institute for Children’s and Women’s Health, Vancouver, British Columbia, Canada
LL-37 is a cationic peptide that is found in the granules of neutrophils and is secreted by epithelial cells from a variety of tissues. Levels of LL-37 in vivo increase upon infection, and its production and secretion are increased upon stimulation with proinflammatory mediators. It has been postulated that LL-37 modulates the immune response by interacting with the effector cells of innate immunity; however, the mechanism of this interaction is unknown. LL-37 induced phosphorylation and activation of the mitogen-activated protein kinases, extracellular signal-regulated kinase 1/2 (ERK1/2) and p38, in human peripheral blood-derived monocytes and a human bronchial epithelial cell line, but not in B or T lymphocytes. Phosphorylation was not dependent on the G protein-coupled formyl peptide-like receptor 1, which was previously proposed to be the receptor for LL-37-induced chemotaxis on human monocytes and T cells. Activation of ERK1/2 and p38 was markedly increased by the presence of GM-CSF, but not M-CSF. Exposure to LL-37 also led to the activation of Elk-1, a transcription factor that is downstream of and activated by phosphorylated ERK1/2, the up-regulation of various Elk-1-controlled genes, and the transcription and secretion of IL-8. Inhibition of either p38 or ERK1/2 kinases led to a reduction in LL-37-induced IL-8 secretion and inhibition of the transcription of various chemokine genes. The ability of LL-37 to signal through these pathways has broad implications in immunity, monocyte activation, proliferation, and differentiation.
This article has been cited by other articles:
|
|
 |
|
  A. Nijnik, J. Pistolic, A. Wyatt, S. Tam, and R. E. W. Hancock Human Cathelicidin Peptide LL-37 Modulates the Effects of IFN-{gamma} on APCs J. Immunol., November 1, 2009; 183(9): 5788 - 5798. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mookherjee, D. N. D. Lippert, P. Hamill, R. Falsafi, A. Nijnik, J. Kindrachuk, J. Pistolic, J. Gardy, P. Miri, M. Naseer, et al. Intracellular Receptor for Human Host Defense Peptide LL-37 in Monocytes J. Immunol., August 15, 2009; 183(4): 2688 - 2696. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Bergsson, E. P. Reeves, P. McNally, S. H. Chotirmall, C. M. Greene, P. Greally, P. Murphy, S. J. O'Neill, and N. G. McElvaney LL-37 Complexation with Glycosaminoglycans in Cystic Fibrosis Lungs Inhibits Antimicrobial Activity, Which Can Be Restored by Hypertonic Saline J. Immunol., July 1, 2009; 183(1): 543 - 551. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. B. Coffelt, S. L. Tomchuck, K. J. Zwezdaryk, E. S. Danka, and A. B. Scandurro Leucine Leucine-37 Uses Formyl Peptide Receptor-Like 1 to Activate Signal Transduction Pathways, Stimulate Oncogenic Gene Expression, and Enhance the Invasiveness of Ovarian Cancer Cells Mol. Cancer Res., June 1, 2009; 7(6): 907 - 915. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 O. Soehnlein and L. Lindbom Neutrophil-derived azurocidin alarms the immune system J. Leukoc. Biol., March 1, 2009; 85(3): 344 - 351. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Cosseau, D. A. Devine, E. Dullaghan, J. L. Gardy, A. Chikatamarla, S. Gellatly, L. L. Yu, J. Pistolic, R. Falsafi, J. Tagg, et al. The Commensal Streptococcus salivarius K12 Downregulates the Innate Immune Responses of Human Epithelial Cells and Promotes Host-Microbe Homeostasis Infect. Immun., September 1, 2008; 76(9): 4163 - 4175. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Di Nardo, K. Yamasaki, R. A. Dorschner, Y. Lai, and R. L. Gallo Mast Cell Cathelicidin Antimicrobial Peptide Prevents Invasive Group A Streptococcus Infection of the Skin J. Immunol., June 1, 2008; 180(11): 7565 - 7573. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. C. K. Cheung, P. V. Turner, C. Song, D. Wu, H. Y. Cai, J. I. MacInnes, and J. Li Enhanced Resistance to Bacterial Infection in Protegrin-1 Transgenic Mice Antimicrob. Agents Chemother., May 1, 2008; 52(5): 1812 - 1819. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Yu, N. Mookherjee, K. Wee, D. M. E. Bowdish, J. Pistolic, Y. Li, L. Rehaume, and R. E. W. Hancock Host Defense Peptide LL-37, in Synergy with Inflammatory Mediator IL-1beta, Augments Immune Responses by Multiple Pathways J. Immunol., December 1, 2007; 179(11): 7684 - 7691. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. C. Huang, R. Y. Reins, R. L. Gallo, and A. M. McDermott Cathelicidin-Deficient (Cnlp / ) Mice Show Increased Susceptibility to Pseudomonas aeruginosa Keratitis Invest. Ophthalmol. Vis. Sci., October 1, 2007; 48(10): 4498 - 4508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Di Nardo, M. H. Braff, K. R. Taylor, C. Na, R. D. Granstein, J. E. McInturff, S. Krutzik, R. L. Modlin, and R. L. Gallo Cathelicidin Antimicrobial Peptides Block Dendritic Cell TLR4 Activation and Allergic Contact Sensitization J. Immunol., February 1, 2007; 178(3): 1829 - 1834. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Davidson, A. J. Currie, D. M. E. Bowdish, K. L. Brown, C. M. Rosenberger, R. C. Ma, J. Bylund, P. A. Campsall, A. Puel, C. Picard, et al. IRAK-4 Mutation (Q293X): Rapid Detection and Characterization of Defective Post-Transcriptional TLR/IL-1R Responses in Human Myeloid and Non-Myeloid Cells J. Immunol., December 1, 2006; 177(11): 8202 - 8211. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Kandler, R. Shaykhiev, P. Kleemann, F. Klescz, M. Lohoff, C. Vogelmeier, and R. Bals The anti-microbial peptide LL-37 inhibits the activation of dendritic cells by TLR ligands Int. Immunol., December 1, 2006; 18(12): 1729 - 1736. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. G. Barlow, Y. Li, T. S. Wilkinson, D. M. E. Bowdish, Y. E. Lau, C. Cosseau, C. Haslett, A. J. Simpson, R. E. W. Hancock, and D. J. Davidson The human cationic host defense peptide LL-37 mediates contrasting effects on apoptotic pathways in different primary cells of the innate immune system J. Leukoc. Biol., September 1, 2006; 80(3): 509 - 520. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. H. Yang, W. K. K. Wu, E. K. K. Tai, H. P. S. Wong, E. K. Y. Lam, W. H. L. So, V. Y. Shin, and C. H. Cho The Cationic Host Defense Peptide rCRAMP Promotes Gastric Ulcer Healing in Rats J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 547 - 554. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Jenssen, P. Hamill, and R. E. W. Hancock Peptide Antimicrobial Agents Clin. Microbiol. Rev., July 1, 2006; 19(3): 491 - 511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. C. Huang, T. D. Petkova, R. Y. Reins, R. J. Proske, and A. M. McDermott Multifunctional Roles of Human Cathelicidin (LL-37) at the Ocular Surface. Invest. Ophthalmol. Vis. Sci., June 1, 2006; 47(6): 2369 - 2380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Cirioni, A. Giacometti, R. Ghiselli, C. Bergnach, F. Orlando, C. Silvestri, F. Mocchegiani, A. Licci, B. Skerlavaj, M. Rocchi, et al. LL-37 Protects Rats against Lethal Sepsis Caused by Gram-Negative Bacteria. Antimicrob. Agents Chemother., May 1, 2006; 50(5): 1672 - 1679. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. E. Lau, D. M. E. Bowdish, C. Cosseau, R. E. W. Hancock, and D. J. Davidson Apoptosis of Airway Epithelial Cells: Human Serum Sensitive Induction by the Cathelicidin LL-37 Am. J. Respir. Cell Mol. Biol., April 1, 2006; 34(4): 399 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mookherjee, K. L. Brown, D. M. E. Bowdish, S. Doria, R. Falsafi, K. Hokamp, F. M. Roche, R. Mu, G. H. Doho, J. Pistolic, et al. Modulation of the TLR-Mediated Inflammatory Response by the Endogenous Human Host Defense Peptide LL-37 J. Immunol., February 15, 2006; 176(4): 2455 - 2464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. C. Taggart, S.-A. Cryan, S. Weldon, A. Gibbons, C. M. Greene, E. Kelly, T. B. Low, S. J. O'Neill, and N. G. McElvaney Secretory leucoprotease inhibitor binds to NF-{kappa}B binding sites in monocytes and inhibits p65 binding J. Exp. Med., December 19, 2005; 202(12): 1659 - 1668. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y.-L. Tzeng, K. D. Ambrose, S. Zughaier, X. Zhou, Y. K. Miller, W. M. Shafer, and D. S. Stephens Cationic Antimicrobial Peptide Resistance in Neisseria meningitidis J. Bacteriol., August 1, 2005; 187(15): 5387 - 5396. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. K. Morgan, R. W. Costello, N. Durcan, P. J. Kingham, G. J. Gleich, W. G. McLean, and M.-T. Walsh Diverse Effects of Eosinophil Cationic Granule Proteins on IMR-32 Nerve Cell Signaling and Survival Am. J. Respir. Cell Mol. Biol., August 1, 2005; 33(2): 169 - 177. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Niyonsaba, H. Ushio, I. Nagaoka, K. Okumura, and H. Ogawa The Human {beta}-Defensins (-1, -2, -3, -4) and Cathelicidin LL-37 Induce IL-18 Secretion through p38 and ERK MAPK Activation in Primary Human Keratinocytes J. Immunol., August 1, 2005; 175(3): 1776 - 1784. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. E. Bowdish, D. J. Davidson, M. G. Scott, and R. E. W. Hancock Immunomodulatory Activities of Small Host Defense Peptides Antimicrob. Agents Chemother., May 1, 2005; 49(5): 1727 - 1732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. M. E. Bowdish, D. J. Davidson, Y. E. Lau, K. Lee, M. G. Scott, and R. E. W. Hancock Impact of LL-37 on anti-infective immunity J. Leukoc. Biol., April 1, 2005; 77(4): 451 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. van Wetering, G. S. Tjabringa, and P. S. Hiemstra Interactions between neutrophil-derived antimicrobial peptides and airway epithelial cells J. Leukoc. Biol., April 1, 2005; 77(4): 444 - 450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. Braff, M. A. Hawkins, A. D. Nardo, B. Lopez-Garcia, M. D. Howell, C. Wong, K. Lin, J. E. Streib, R. Dorschner, D. Y. M. Leung, et al. Structure-Function Relationships among Human Cathelicidin Peptides: Dissociation of Antimicrobial Properties from Host Immunostimulatory Activities J. Immunol., April 1, 2005; 174(7): 4271 - 4278. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
