Antimicrobial peptides (which attack pathogens) are increased by Vitamin D

UC and Cathelicidin - Jan 2020

Cathelicidin Mediates a Protective Role of Vitamin D in Ulcerative Colitis and Human Colonic Epithelial Cells
Inflamm Bowel Dis, 2020 PMID: 31955203 DOI: 10.1093/ibd/izz330
John Gubatan 1 2, Gillian A Mehigan 1, Fernando Villegas 1, Shuji Mitsuhashi 1, Maria Serena Longhi 1, Grace Malvar 3, Eva Csizmadia 1, Simon Robson 1, Alan C Moss 1

Background: Vitamin D plays a protective role in ulcerative colitis (UC) patients through unclear mechanisms. Cathelicidin is an antimicrobial peptide induced by 1,25(OH)D2. Our goal was to evaluate the link between cathelicidin and vitamin D-associated clinical outcomes in UC patients, explore vitamin D induction of cathelicidin in human colon cells, and evaluate the effects of intrarectal human cathelicidin on a murine model of colitis.

Methods: Serum and colonic cathelicidin levels were measured in UC patients and correlated with clinical and histologic outcomes. Human colon cells were treated with 1,25(OH)2D and production of cathelicidin and cytokines were quantified. Antimicrobial activity against Escherichia coli from cell culture supernatants was measured. Mice were treated with intrarectal cathelicidin, and its effects on DSS colitis and intestinal microbiota were evaluated.

Results: In UC patients, serum 25(OH)D positively correlated with serum and colonic cathelicidin. Higher serum cathelicidin is associated with decreased risk of histologic inflammation and clinical relapse but not independent of 25(OH)D or baseline inflammation. The 1,25(OH)2D treatment of colon cells induced cathelicidin and IL-10, repressed TNF-α, and suppressed Escherichia coli growth. This antimicrobial effect was attenuated with siRNA-cathelicidin transfection. Intrarectal cathelicidin reduced the severity of DSS colitis but did not mitigate the impact of colitis on microbial composition.

Conclusions: Cathelicidin plays a protective role in 25(OH)D-associated UC histologic outcomes and murine colitis. Cathelicidin is induced by vitamin D in human colonic epithelial cells and promotes antimicrobial activity against E. coli. Our study provides insights into the vitamin D-cathelicidin pathway as a potential therapeutic target.

Human Antimicrobial Peptides and Proteins - 2014

Pharmaceuticals (Basel). May 2014; 7(5): 545–594. doi: 10.3390/ph7050545
Guangshun Wang

As the key components of innate immunity, human host defense antimicrobial peptides and proteins (AMPs) play a critical role in warding off invading microbial pathogens.
In addition, AMPs can possess other biological functions such as

  • apoptosis,
  • wound healing, and
  • immune modulation.

This article provides an overview on the identification, activity, 3D structure, and mechanism of action of human AMPs selected from the antimicrobial peptide database.
Over 100 such peptides have been identified from a variety of tissues and epithelial surfaces, including

  • skin,
  • eyes,
  • ears,
  • mouths,
  • gut,
  • immune,
  • nervous and
  • urinary systems.

These peptides vary from 10 to 150 amino acids with a net charge between −3 and +20 and a hydrophobic content below 60%. The sequence diversity enables human AMPs to adopt various 3D structures and to attack pathogens by different mechanisms. While α-defensin HD-6 can self-assemble on the bacterial surface into nanonets to entangle bacteria, both HNP-1 and β-defensin hBD-3 are able to block cell wall biosynthesis by binding to lipid II. Lysozyme is well-characterized to cleave bacterial cell wall polysaccharides but can also kill bacteria by a non-catalytic mechanism. The two hydrophobic domains in the long amphipathic α-helix of human cathelicidin LL-37 lays the basis for binding and disrupting the curved anionic bacterial membrane surfaces by forming pores or via the carpet model. Furthermore, dermcidin may serve as ion channel by forming a long helix-bundle structure. In addition, the C-type lectin RegIIIα can initially recognize bacterial peptidoglycans followed by pore formation in the membrane. Finally, histatin 5 and GAPDH(2-32) can enter microbial cells to exert their effects. It appears that granulysin enters cells and kills intracellular pathogens with the aid of pore-forming perforin. This arsenal of human defense proteins not only keeps us healthy but also inspires the development of a new generation of personalized medicine to combat drug-resistant superbugs, fungi, viruses, parasites, or cancer. Alternatively, multiple factors (e.g., albumin, arginine, butyrate, calcium, cyclic AMP, isoleucine, short-chain fatty acids, UV B light, vitamin D, and zinc) are able to induce the expression of antimicrobial peptides, opening new avenues to the development of anti-infectious drugs.

 Download the PDF from VitaminDWiki.
Thanks goes to Edward Hutchinson for pointing out this article

5,000 IU of Vitamin D increased antimicrobial peptides and proteins in athletes- Aug 2016

The effect of 14 weeks of vitamin D3 supplementation on antimicrobial peptides and proteins in athletes. -
J Sports Sci. 2016;34(1):67-74. doi: 10.1080/02640414.2015.1033642. Epub 2015 Apr 10.
He CS1, Fraser WD2,3, Tang J2, Brown K1, Renwick S1, Rudland-Thomas J1, Teah J1, Tanqueray E1, Gleeson M1.
1a School of Sport, Exercise and Health Sciences , Loughborough University , Loughborough , Leicestershire LE11 3TU , UK.
2b Norwich Medical School, Faculty of Medicine and Health Sciences , University of East Anglia , Norwich NR4 7TJ , UK.
3c Norfolk and Norwich University Hospital , Norwich NR4 7UY , UK.

Heavy training is associated with increased respiratory infection risk and antimicrobial proteins are important in defence against oral and respiratory tract infections. We examined the effect of 14 weeks of vitamin D3 supplementation (5000 IU/day) on the resting plasma cathelicidin concentration and the salivary secretion rates of secretory immunoglobulin A (SIgA), cathelicidin, lactoferrin and lysozyme in athletes during a winter training period. Blood and saliva were obtained at the start of the study from 39 healthy men who were randomly allocated to vitamin D3 supplement or placebo. Blood samples were also collected at the end of the study; saliva samples were collected after 7 and 14 weeks. Plasma total 25(OH)D concentration increased by 130% in the vitamin D3 group and decreased by 43% in the placebo group (both P = 0.001). The percentage change of plasma cathelicidin concentration in the vitamin D3 group was higher than in the placebo group (P = 0.025).
Only in the vitamin D3 group, the saliva SIgA and cathelicidin secretion rates increased over time (both P = 0.03).
A daily 5000 IU vitamin D3 supplement has a beneficial effect in up-regulating the expression of SIgA and cathelicidin in athletes during a winter training period, which could improve resistance to respiratory infections.

PMID: 25861808 DOI: 10.1080/02640414.2015.1033642
 Download the PDF from Sci-Hub VitaminDWiki

Thanks goes to Dr. Raimund von Helden, Family Physician for his web page on cathelicidin and E-coli in Germany
CLICK HERE for his German web page in any language (starts with English)

cathelicidin antimicrobial protein-18   =   hCAP18   =   LL-37

Vitamin D, Immune Response May Reduce Fatal Infections in Dialysis Patients March 2009

Link
CORVALLIS, Ore. – Higher levels of a certain antimicrobial protein that’s regulated by vitamin D appear to significantly reduce the risk of death from infection in dialysis patients, a new study has found.

Patients with a high level of this protein were 3.7 times more likely to survive kidney dialysis for a year without a fatal infection, which is a constant concern with dialysis patients.
Death from infection is 100 to 300 times higher for dialysis E than for most people.

The research was done by scientists from the Linus Pauling Institute at Oregon State University, Cedars-Sinai Medical Center, Harvard Medical School and the University of Copenhagen. It was published in Clinical Infectious Diseases, a professional journal.

This protein, called human cathelicidin antimicrobial protein, or hCAP18, is part of the “innate” immune system in humans, a mechanism that helps fight off various bacteria, viruses and fungi even though they have never been encountered before. These “antimicrobial peptides” have been the source of considerable research in recent years, in part because pathogens rarely develop resistance to them.

“The two primary killers of dialysis patients are heart attacks and infections, which often begin around catheters,” said Adrian Gombart, an expert on vitamin D and associate professor in the Linus Pauling Institute. “If hCAP18 is directly responsible for increases in survival, therapies that increase its levels might be a good adjunct to traditional antibiotics to address this problem.”

This study looked at 279 patients across the nation with end-stage renal disease who were being treated with dialysis – a situation facing about 300,000 people in the United States. People with severe kidney disease often have immune systems that are out of balance, as well as low levels of vitamin D, which plays a key role in the immune response. It had been found earlier that administration of active vitamin D analogues to patients undergoing hemodialysis could reduce their mortality rate, but the mechanisms are not understood.

The peptide hCAP18 is of particular interest, Gombart said, because it’s the only known antimicrobial peptide of this type in humans. It appears to have the ability to kill a broad range of bacteria, including those that cause tuberculosis and protect against the development of sepsis. This peptide is regulated in the body by vitamin D, and it’s believed that vitamin D therapy may be one mechanism that could boost hCAP18 levels.

The study found that plasma levels of hCAP18 in the dialysis patients were on average about half that of healthy individuals, and that those with the very lowest levels were almost four times as likely to die from infection within a year.

Further studies are needed of the mechanisms of disease prevention with these patients, the researchers said, and whether vitamin D or other therapies can raise hCAP18 levels in these patients and improve their overall survival.

This study may also be useful, Gombart said, to help physicians identify dialysis patients who are at greatest risk of infection, and be able to address those problems quickly.

This research was supported by the National Kidney Foundation and the National Institutes of Health.

About the Linus Pauling Institute: The Linus Pauling Institute at OSU is a world leader in the study of micronutrients and their role in promoting optimum health or preventing and treating disease. Major areas of research include heart disease, cancer, aging and neurodegenerative disease.

By (source) Adrian Gombart, 541-737-8018, Contact: David Stauth, 541-737-0787

See also VitaminDWiki

See also web

  • Vitamin D-Cathelicidin Axis: at the Crossroads between Protective Immunity and Pathological Inflammation during Infection - Feb 2020 - doi: 10.4110/in.2020.20.e12  PDF

Cathelicidin "Vitamin D" 465 PubMed items as of Nov 2023

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