Protective effects of Cathelicidin against glomerulonephritis through promotion of host defense



Cathelicidin-related antimicrobial peptides are a family of polypeptides found in lysosomes of macrophages and polymorphonuclear leukocytes (PMNs). Some of these peptides can assume an alpha-helical conformation, others contain one or two disulfide bonds, still others are Pro- and Arg-rich, or Trp-rich. Higher levels of human cathelicidin antimicrobial protein (hCAP18), which are up-regulated by vitamin D, appear to significantly reduce the risk of death from infection in dialysis patients. Using in vitro and in vivo models of kidney infection, we demonstrate key antimicrobial and host immunomodulatory properties of cathelicidins. To directly assess the role of endogenous cathelicidin in the development of glomerulonephritis, WT and mCRAMP KO mice were provided with 5% DSS to induce glomerulonephritis. Some mice groups were administered with E. coli DNA I.P. Our findings showed that mCRAMP KO mice develop more severe glomerulonephritis. These data demonstrate key roles for cathelicidins in host defense against glomerulonephritis and the potential to inform the development of synthetic analogues to modulate specific host-pathogen interactions as novel antimicrobial therapeutics.

Key words: Cathelicidin; Glomerulonephritis; E. coli DNA; mCRAMP KO mice

Copyright © 2014 by The American Society for BioMedicine and BM-Publisher, Inc.

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  1. Zhang Y, Shi W, Tang S, et al. The influence of cathelicidin LL37 in human anti-neutrophils cytoplasmic antibody (ANCA)-associated vasculitis. Arthritis Res Ther. 2013;16:R161.
  2. Gordon YJ, Huang LC, Romanowski EG, et al. Human cathelicidin (LL-37), a multifunctional peptide, is expressed by ocular surface epithelia and has potent antibacterial and antiviral activity. Curr Eye Res. 2005;30:385–394.
  3. Bourcier T, Thomas F, Borderie V, et al. Bacterial keratitis: predisposing factors, clinical and microbiological review of 300 cases. Br J Ophthalmol. 2003;87:834–838.
  4. Kittaka M, Shiba H, Kajiya M, et al. Antimicrobial peptide LL37 promotes vascular endothelial growth factor-a expression in human periodontal ligament cells. J Periodontal Res. 2013;16:228–234.
  5. Hase K, Murakami M, Iimura M, et al. Expression of LL-37 by human gastric epithelial cells as a potential host defense mechanism against Helicobacter pylori. Gastroenterology. 2003;125:1613–1625.
  6. Mela EK, Giannelou IP, Koliopoulos JX, et al. Ulcerative keratitis in contact lens wearers. Eye Contact Lens. 2003;29:207–209.
  7. Jennette JC, Xiao H, Falk R, Gasim AM. Experimental models of vasculitis and glomerulonephritis induced by antineutrophil cytoplasmic autoantibodies. Contrib Nephrol. 2011;16:211–220.
  8. De Y, Chen Q, Schmidt AP, et al. LL-37, the neutrophil granule- and epithelial cell-derived cathelicidin, utilizes formyl peptide receptor-like 1 (FPRL1) as a receptor to chemoattract human peripheral blood neutrophils, monocytes, and T cells. J Exp Med. 2000;192:1069–1074.
  9. Cole N, Willcox MD, Fleiszig SM, et al. Different strains of Pseudomonas aeruginosa isolated from ocular infections or inflammation display distinct corneal pathologies in an animal model. Curr Eye Res. 1998;17:730–735.
  10. Dombrowski Y, Schauber J. Cathelicidin LL-37: a defense molecule with a potential role in psoriasis pathogenesis. Exp Dermatol. 2012;16:327–330.
  11. Gilla K, Mohantib BK, Singha AK, Mishraa B, Deya S. The over expression of cathelicidin peptide LL37 in head and neck squamous cell carcinoma: the peptide marker for the prognosis of cancer. Cancer Biomarkers. 2012;16:125–134.
  12. Pestonjamasp VK, Huttner KH, Gallo RL. Processing site and gene structure for the murine antimicrobial peptide CRAMP. Peptides. 2001;22:1643–1650.
  13. Fleiszig SM, Evans DJ. The pathogenesis of bacterial keratitis: studies with Pseudomonas aeruginosa. Clin Exp Optom. 2002;85:271–278.
  14. Kessenbrock K, Krumbholz M, Schönermarck U, Back W, Gross WL, Werb Z, Gröne HJ, Brinkmann V, Jenne DE. Netting neutrophils in autoimmune small-vessel vasculitis. Nat Med. 2009;16:623–625.
  15. Nagaoka I, Hirota S, Niyonsaba F, et al. Augmentation of the lipopolysaccharide-neutralizing activities of human cathelicidin CAP18/LL-37-derived antimicrobial peptides by replacement with hydrophobic and cationic amino acid residues. Clin Diagn Lab Immunol. 2002;9:972–982.
  16. Bandholtz L, Ekman GJ, Vilhelmsson M, et al. Antimicrobial peptide LL-37 internalized by immature human dendritic cells alters their phenotype. Scand J Immunol. 2006;63:410–419.
  17. Kaplan-Pavlovcic S, Cerk K, Kveder R, Lindic J, Vizjak A. Clinical prognostic factors of renal outcome in anti-neutrophil cytoplasmic autoantibody (ANCA)-associated glomerulonephritis in elderly patients. Nephrol Dial Transplant. 2003;16:v5–v7.
  18. Kernacki KA, Fridman R, Hazlett LD, et al. In vivo characterization of host and bacterial protease expression during Pseudomonas aeruginosa corneal infections in naive and immunized mice. Curr Eye Res. 1997;16:289–297.
  19. Slot MC, Tervaert JW, Franssen CF, Stegeman CA. Renal survival and prognostic factors in patients with PR3-ANCA associated vasculitis with renal involvement. Kidney Int. 2003;16:670–677.
  20. Lionaki S, Blyth ER, Hogan SL, et al. Classification of antineutrophil cytoplasmic autoantibody vasculitides: the role of antineutrophil cytoplasmic autoantibody specificity for myeloperoxidase or proteinase 3 in disease recognition and prognosis. Arthritis Rheum. 2012;16:3452–3462.
  21. Torres PF, Kijlstra A. The role of cytokines in corneal immunopathology. Ocul Immunol Inflamm. 2001;9:9–24.
  22. Bowdish DM, Davidson DJ, Speert DP, et al. The human cationic peptide LL-37 induces activation of the extracellular signal-regulated kinase and p38 kinase pathways in primary human monocytes. J Immunol. 2004;172:3758–3765.
  23. Specks U. Controversies in ANCA testing. Cleve Clin J Med. 2012;16:S7–S11.
  24. Roth AJ, Ooi JD, Hess JJ, et al. Epitope specificity determines pathogenicity and detectability in ANCA-associated vasculitis. J Clin Invest. 2013;16:1773–1783.
  25. Murakami M, Ohtake T, Dorschner RA, et al. Cathelicidin antimicrobial peptides are expressed in salivary glands and saliva. J Dent Res. 2002;81:845–850.
  26. Rosenberger CM, Gallo RL, Finlay BB. Interplay between antibacterial effectors: a macrophage antimicrobial peptide impairs intracellular Salmonella replication. Proc Natl Acad Sci USA. 2004;101:2422–2427.
  27. Berden AE, Ferrario F, Hagen EC, et al. Histopathologic classification of ANCA-associated glomerulonephritis. J Am Soc Nephrol. 2010;16:1628–1636.
  28. Barak O, Treat JR, James WD. Antimicrobial peptides: effectors of innate immunity in the skin. Adv Dermatol. 2005;21:357–374.

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Review Article
American Journal of BioMedicine 2014, Volume 2, Issue 3, pages 189-198
Received 11 March 2014; accepted June 21, 2014, Published August 30, 2014

How to cite this article
Bahl AH, Lee W, Song SJ, Geren NR, Haas CM, Ekong YH, Wittmann GD. Protective effects of Cathelicidin against glomerulonephritis through promotion of host defense. American Journal of BioMedicine 2014;2(3):189-198.

Case report outline
1. Abstract
2. Keywords
3. Introduction
4. Methods
5. Results
6. Discussion
7. References

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