| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of
*
Pulmonology, and
Immunohematology and Bloodtransfusion, Leiden University Medical Center, Leiden, The Netherlands; and
The Granulocyte Research Laboratory, Department of Hematology, Copenhagen University Hospital, Copenhagen, Denmark
Antimicrobial peptides produced by epithelial cells and neutrophils represent essential elements of innate immunity, and include the defensin and cathelicidin family of antimicrobial polypeptides. The human cathelicidin cationic antimicrobial protein-18 is an antimicrobial peptide precursor predominantly expressed in neutrophils, and its active peptide LL-37 is released from the precursor through the action of neutrophil serine proteinases. LL-37 has been shown to display antimicrobial activity against a broad spectrum of microorganisms, to neutralize LPS bioactivity, and to chemoattract neutrophils, monocytes, mast cells, and T cells. In this study we show that LL-37 activates airway epithelial cells as demonstrated by activation of the mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK) and increased release of IL-8. Epithelial cell activation was inhibited by the MAPK/ERK kinase (MEK) inhibitors PD98059 and U0126, by the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478, by blocking anti-EGFR and anti-EGFR-ligand Abs, and by the metalloproteinase inhibitor GM6001. These data suggest that LL-37 transactivates the EGFR via metalloproteinase-mediated cleavage of membrane-anchored EGFR-ligands. LL-37 may thus constitute one of the mediators by which neutrophils regulate epithelial cell activity in the lung.
This article has been cited by other articles:
|
|
 |
|
  M. J. Oudhoff, J. G. M. Bolscher, K. Nazmi, H. Kalay, W. van 't Hof, A. V. N. Amerongen, and E. C. I. Veerman Histatins are the major wound-closure stimulating factors in human saliva as identified in a cell culture assay FASEB J, November 1, 2008; 22(11): 3805 - 3812. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Diamond, N. Beckloff, and L.K. Ryan Host Defense Peptides in the Oral Cavity and the Lung: Similarities and Differences J. Dent. Res., October 1, 2008; 87(10): 915 - 927. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Overhage, A. Campisano, M. Bains, E. C. W. Torfs, B. H. A. Rehm, and R. E. W. Hancock Human Host Defense Peptide LL-37 Prevents Bacterial Biofilm Formation Infect. Immun., September 1, 2008; 76(9): 4176 - 4182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Zhang, G. Cherryholmes, and J. E. Shively Neutrophil secondary necrosis is induced by LL-37 derived from cathelicidin J. Leukoc. Biol., September 1, 2008; 84(3): 780 - 788. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Mendez-Samperio, E. Miranda, and A. Trejo Expression and Secretion of Cathelicidin LL-37 in Human Epithelial Cells after Infection by Mycobacterium bovis Bacillus Calmette-Guerin Clin. Vaccine Immunol., September 1, 2008; 15(9): 1450 - 1455. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bucki, D. B. Namiot, Z. Namiot, P. B. Savage, and P. A. Janmey Salivary mucins inhibit antibacterial activity of the cathelicidin-derived LL-37 peptide but not the cationic steroid CSA-13 J. Antimicrob. Chemother., August 1, 2008; 62(2): 329 - 335. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. L. Koff, M. X. G. Shao, I. F. Ueki, and J. A. Nadel Multiple TLRs activate EGFR via a signaling cascade to produce innate immune responses in airway epithelium Am J Physiol Lung Cell Mol Physiol, June 1, 2008; 294(6): L1068 - L1075. [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]
|
|
|
|
 |
|
 E. K. K. Tai, W. K. K. Wu, H. P. S. Wong, E. K. Y. Lam, L. Yu, and C. H. Cho A New Role for Cathelicidin in Ulcerative Colitis in Mice Experimental Biology and Medicine, June 1, 2007; 232(6): 799 - 808. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Koff, M. X. G. Shao, S. Kim, I. F. Ueki, and J. A. Nadel Pseudomonas Lipopolysaccharide Accelerates Wound Repair via Activation of a Novel Epithelial Cell Signaling Cascade J. Immunol., December 15, 2006; 177(12): 8693 - 8700. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Zuyderduyn, DennisK. Ninaber, PieterS. Hiemstra, and KlausF. Rabe Role of purinergic receptors in the activation of human airway smooth muscle cells by the antimicrobial peptide LL-37 Eur. Respir. Rev., December 1, 2006; 15(101): 182 - 184. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Mookherjee, H. L. Wilson, S. Doria, Y. Popowych, R. Falsafi, J. Yu, Y. Li, S. Veatch, F. M. Roche, K. L. Brown, et al. Bovine and human cathelicidin cationic host defense peptides similarly suppress transcriptional responses to bacterial lipopolysaccharide J. Leukoc. Biol., December 1, 2006; 80(6): 1563 - 1574. [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]
|
|
|
|
|
|
K. Yamasaki, J. Schauber, A. Coda, H. Lin, R. A. Dorschner, N. M. Schechter, C. Bonnart, P. Descargues, A. Hovnanian, and R. L. Gallo Kallikrein-mediated proteolysis regulates the antimicrobial effects of cathelicidins in skin FASEB J, October 1, 2006; 20(12): 2068 - 2080. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Bucki and P. A. Janmey Interaction of the Gelsolin-Derived Antibacterial PBP 10 Peptide with Lipid Bilayers and Cell Membranes. Antimicrob. Agents Chemother., September 1, 2006; 50(9): 2932 - 2940. [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]
|
|
|
|
 |
|
 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]
|
|
|
|
 |
|
 S. Pochet, S. Tandel, S. Querriere, M. Tre-Hardy, M. Garcia-Marcos, M. De Lorenzi, M. Vandenbranden, A. Marino, M. Devleeschouwer, and J.-P. Dehaye Modulation by LL-37 of the Responses of Salivary Glands to Purinergic Agonists Mol. Pharmacol., June 1, 2006; 69(6): 2037 - 2046. [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]
|
|
|
|
|
|
I. Nagaoka, H. Tamura, and M. Hirata An Antimicrobial Cathelicidin Peptide, Human CAP18/LL-37, Suppresses Neutrophil Apoptosis via the Activation of Formyl-Peptide Receptor-Like 1 and P2X7. J. Immunol., March 1, 2006; 176(5): 3044 - 3052. [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.-Y. Kao, F. Huang, Y. Chen, P. Thai, S. Wachi, C. Kim, L. Tam, and R. Wu Up-Regulation of CC Chemokine Ligand 20 Expression in Human Airway Epithelium by IL-17 through a JAK-Independent but MEK/NF-{kappa}B-Dependent Signaling Pathway J. Immunol., November 15, 2005; 175(10): 6676 - 6685. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Shaykhiev, C. Beisswenger, K. Kandler, J. Senske, A. Puchner, T. Damm, J. Behr, and R. Bals Human endogenous antibiotic LL-37 stimulates airway epithelial cell proliferation and wound closure Am J Physiol Lung Cell Mol Physiol, November 1, 2005; 289(5): L842 - L848. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Tokumaru, K. Sayama, Y. Shirakata, H. Komatsuzawa, K. Ouhara, Y. Hanakawa, Y. Yahata, X. Dai, M. Tohyama, H. Nagai, et al. Induction of Keratinocyte Migration via Transactivation of the Epidermal Growth Factor Receptor by the Antimicrobial Peptide LL-37 J. Immunol., October 1, 2005; 175(7): 4662 - 4668. [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, 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]
|
|
|
|
|
|
N. Borregaard, K. Theilgaard-Monch, J. B. Cowland, M. Stahle, and O. E. Sorensen Neutrophils and keratinocytes in innate immunity--cooperative actions to provide antimicrobial defense at the right time and place J. Leukoc. Biol., April 1, 2005; 77(4): 439 - 443. [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]
|
|
|
|
|
|
Y. E. Lau, A. Rozek, M. G. Scott, D. L. Goosney, D. J. Davidson, and R. E. W. Hancock Interaction and Cellular Localization of the Human Host Defense Peptide LL-37 with Lung Epithelial Cells Infect. Immun., January 1, 2005; 73(1): 583 - 591. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
O. Levy Antimicrobial proteins and peptides: anti-infective molecules of mammalian leukocytes J. Leukoc. Biol., November 1, 2004; 76(5): 909 - 925. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
