Cathelicidin LL-37: An Antimicrobial Peptide with a Role in Inflammatory Skin Disease

Reinholz, Markus; Ruzicka, Thomas; Schauber, Jürgen

doi:10.5021/ad.2012.24.2.126

Cited by 199 publications

(161 citation statements)

References 78 publications

Supporting

Mentioning

151

Contrasting

Unclassified

Order By: Relevance

“…Dysfunction of cathelicidin LL-37, a molecule proven to play a central role in innate cutaneous immunity, is expressed in all three of these diseases (25).…”

Section: Discussionmentioning

confidence: 99%

Mycotic Pseudoaneurysm of the Femoral Artery in a Patient with Psoriasis

2012

View full text Add to dashboard Cite

Mycotic aneurysms of the common femoral artery are rare and usually occur in intravenous drug abusers who use the femoral vessels for injection. We herein describe a case of mycotic aneurysm of the common femoral artery caused by methicillin-sensitive Staphylococcus aureus seeding of an atherosclerotic plaque in which the bacteria possibly originated from psoriatic skin lesions. A 67-year-old Caucasian man was admitted to the hospital after experiencing chest pain for two days. He was known to have psoriasis and coronary artery disease with a history of coronary artery bypass grafting surgery three years earlier. He was found to have methicillin-sensitive Staphylococcus aureus bacteremia and later developed a mycotic aneurysm of the femoral artery opposite to the site of catheterization access. Mycotic aneurysms are rare clinical conditions associated with significant morbidity and mortality. In patients with psoriasis, a high prevalence of Staphylococcus aureus colonization of the skin makes possible bacterial seeding of existing atherosclerotic plaques. Therefore, the risk of mycotic pseudoaneurysm formation in these patients should be considered.

show abstract

“…Dysfunction of cathelicidin LL-37, a molecule proven to play a central role in innate cutaneous immunity, is expressed in all three of these diseases (25).…”

Section: Discussionmentioning

confidence: 99%

Mycotic Pseudoaneurysm of the Femoral Artery in a Patient with Psoriasis

2012

View full text Add to dashboard Cite

show abstract

“…This peptide is expressed in many types of immune and epithelial cells and plays multiple roles in modulating host cellular responses to microbial attack (8). The physiological concentration of LL-37 varies between different cells and tissues and is often altered at infection sites (9)(10)(11)(12). The main antibacterial functions of LL-37 disrupt the microbial cell membrane, which results in cytoplasm leakage (13).…”

mentioning

confidence: 99%

Inactivation of the Antifungal and Immunomodulatory Properties of Human Cathelicidin LL-37 by Aspartic Proteases Produced by the Pathogenic Yeast Candida albicans

et al. 2015

View full text Add to dashboard Cite

c Constant cross talk between Candida albicans yeast cells and their human host determines the outcome of fungal colonization and, eventually, the progress of infectious disease (candidiasis). An effective weapon used by C. albicans to cope with the host defense system is the release of 10 distinct secreted aspartic proteases (SAPs). Here, we validate a hypothesis that neutrophils and epithelial cells use the antimicrobial peptide LL-37 to inactivate C. albicans at sites of candidal infection and that C. albicans uses SAPs to effectively degrade LL-37. LL-37 is cleaved into multiple products by SAP1 to -4, SAP8, and SAP9, and this proteolytic processing is correlated with the gradual decrease in the antifungal activity of LL-37. Moreover, a major intermediate of LL-37 cleavage-the LL-25 peptide-is antifungal but devoid of the immunomodulatory properties of LL-37. In contrast to LL-37, LL-25 did not affect the generation of reactive oxygen species by neutrophils upon treatment with phorbol esters. Stimulating neutrophils with LL-25 (rather than LL-37) significantly decreased calcium flux and interleukin-8 production, resulting in lower chemotactic activity of the peptide against neutrophils, which may decrease the recruitment of neutrophils to infection foci. LL-25 also lost the function of LL-37 as an inhibitor of neutrophil apoptosis, thereby reducing the life span of these defense cells. This study indicates that C. albicans can effectively use aspartic proteases to destroy the antimicrobial and immunomodulatory properties of LL-37, thus enabling the pathogen to survive and propagate.A s a polymorphic opportunistic fungal pathogen, Candida albicans colonizes distinct niches in the human body such as the oral and vaginal cavities and the gut. In healthy individuals, C. albicans is controlled by the host immune system, epithelial barriers, and coexisting commensal microorganisms (1). However, under certain circumstances, C. albicans causes relatively easily curable superficial infections, as well as life-threatening deepseated and disseminated candidiases (2). The transition of C. albicans from a commensal to a pathogen depends mostly on the status of the host's immune system; therefore, the major risk factors for candidiasis include immunosuppressive therapy, indwelling vascular catheters, neutropenia, and prolonged treatment with broad-spectrum antibiotics (3). The pathogenic potential of C. albicans is determined by several factors, including molecules that mediate adhesion to and invasion of host cells, secreted hydrolases, polymorphisms, biofilm formation, and adaptation to stressful environmental conditions within the host organism (4).Neutrophils, which constitute the first line of host defense against microbial pathogens, are recruited to the infection site, where they rapidly respond with diverse antimicrobial mechanisms that demonstrate both intra-and extracellular processes such as phagocytosis and the degranulation and formation of neutrophil extracellular traps (NETs) (5). All of these processes inv...

show abstract

“…21,22 Elevated levels of cathelicidins and abnormal forms of cathelicidins have been reported in patients with rosacea, as well as in those with other inflammatory skin conditions. [23][24][25] Some forms of these cathelicidin peptides have vasoactive and proinflammatory activities leading to modification of dermal structures through vascular changes and collagen degeneration. 26,27 Cathelicidins are processed by an epidermal serine protease called kallikrein 5 (KLK5).…”

Section: ■■ Pathophysiology Of Rosacea Chronic Inflammationmentioning

confidence: 99%