Cathelicidin Antimicrobial Peptides are Expressed in Salivary Glands and Saliva

Murakami, Masamoto; Ohtake, Takaaki; Dorschner, Robert A.; Gallo, Richard L.

doi:10.1177/154405910208101210

Cited by 192 publications

(146 citation statements)

References 33 publications

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“…In the human, LL37 was detected in saliva (Murakami et al, 2002). The results suggest localized expression of different antimicrobial peptides in salivary glands and ducts, similar to that of the gingiva (see above).…”

Section: Ll-37supporting

confidence: 53%

“…The cathelicidin, LL-37, is expressed in epithelial cells especially following inflammatory stimulation, and both the protein and mRNA have been detected in human tongue and buccal mucosa (Frohm Nilsson et al, 1999) and saliva (Murakami et al, 2002). However, LL-37 detected in gingival epithelium by immunohistochemisty appeared to be the product of neutrophil migration through the tissue rather than the epithelial cells per se .…”

Section: Ll-37 and α-Defensinsmentioning

confidence: 99%

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Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease

2005

Current Issues in Molecular Biology

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The oral cavity is a unique environment in which antimicrobial peptides play a key role in maintaining health and may have future therapeutic applications. Present evidence suggests that α-defensins, β-defensins, LL-37, histatin, and other antimicrobial peptides and proteins have distinct but overlapping roles in maintaining oral health and preventing bacterial, fungal, and viral adherence and infection. The expression of the inducible hBD-2 in normal oral epithelium, in contrast to other epithelia, and the apparent differential signaling in response to commensal and pathogenic organisms, provides new insights into innate immunity in this body site. Commensal bacteria are excellent inducers of hBD-2 in oral epithelial cells, suggesting that the commensal bacterial community acts in a manner to benefit the overall innate immune readiness of oral epithelia. This may have major significance for understanding host defense in the complex oral environment. The oral environmentThe oral cavity is a unique environment. Oral mucosa is a critical protective interface between external and internal environments and must serve as a barrier to the myriad microbial species present in this warm, moist environment. The oral cavity is the only area of the body in which hard tissues break through the epithelial surface. The periodontal epithelium surrounding the tooth is specialized to form an attachment and seal around each tooth. This unique function imparts special challenges to the tissue and leads to certain vulnerabilities associated with periodontal disease, especially in view of the continual exposure to the bacterial biofilm (dental plaque) that forms on the tooth surface at the junction of the soft tissue. Thus, this anatomical region is one where there is a significant risk of bacterially induced infection and inflammation.Antimicrobial peptides are important contributors to maintaining the balance between health and disease in this complex environment. These include several salivary antimicrobial peptides, the β-defensins expressed in the epithelium, the α-defensins expressed in neutrophils, and the cathelicidin, LL-37, expressed in both epithelium and neutrophils. These peptides are part of the host innate immune response in this environment. Epithelia, polymorphonuclear leukocytes (neutrophils), and saliva all contribute to the maintaining the health of the oral cavity in overlapping but independent ways. This review will focus on the human oral cavity and include 1) the expression and function of antimicrobial peptides in the oral cavity in the context of innate immune responses, 2) regulation of β-defensins which has led to advances in our understanding of oral epithelial innate immunity, and 3) functional efficacy against oral microbes when it is known. Epithelial antimicrobial peptidesHistorically, the oral epithelium has been considered mainly as a passive covering that becomes damaged and ulcerated in disease. This view has changed dramatically and the epithelial compartment is now seen as providing both...

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Section: Ll-37supporting

confidence: 53%

Section: Ll-37 and α-Defensinsmentioning

confidence: 99%

Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease

2005

Current Issues in Molecular Biology

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“…[7][8][9][10] Constitutive expression of antimicrobial peptides has previously been detected in various exocrine glands such as the human cathelicidin LL-37 in sweat glands, the cathelicidin CRAMP in murine salivary glands and ␤-defensins in human salivary glands. [21][22][23] Expression of human ␤-defensin-2 (hBD-2) mRNA in mammary glands was reported by Bals et al 24 in 1998 and recently other groups have found constitutive hBD-1 expression in mammary glandular tissue of nonlactating women as well as in breast tissue during lactation and in breast milk. 25,26 Our finding that hCAP18/LL-37 is expressed in breast cancer cells is novel.…”

Section: Discussionmentioning

confidence: 93%

Antimicrobial protein hCAP18/LL‐37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells

Heilborn

Nilsson

Jimenez

et al. 2005

Intl Journal of Cancer

112

110

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Human cathelicidin antimicrobial protein hCAP18/LL-37 is an effector molecule of the nonspecific innate immune system. hCAP18/LL-37 is present in leukocytes and is expressed in skin and other epithelia, where it is upregulated in association with inflammation and injury. In addition, antimicrobial proteins including cathelicidins have been proposed to play a role in the nonspecific defense against tumors. To assess its potential role in tumor host defense, we investigated the expression of hCAP18/ LL-37 in a series of breast carcinomas. Unexpectedly, we found that hCAP18/LL-37 was strongly expressed in the tumor cells and not in the adjacent stroma. To test the hypothesis that hCAP18/ LL-37 may provide a growth advantage for the tumor cells, we treated human epithelial cell lines with synthetic biologically active LL-37 peptide and found a significant increase in cell proliferation. In addition, transgenic expression of hCAP18 in 2 different human epithelial cell lines resulted in increased proliferation of both cell types. These findings do not support the hypothesis that LL-37 has an antitumor effect, but rather suggest that hCAP18/LL-37 may promote tumor cell growth in breast cancer.

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“…Neutrophils are a particularly rich source of cathelicidins in a variety of species. In humans, cathelicidins have also been found to be expressed in several other tissues, including the testis (Agerberth et al 1995;Malm et al 2000), squamous epithelia (Frohm Nilsson et al 1999;Nizet et al 2001), airway epithelia (Bals et al 1998), sweat glands (Murakami et al 2002b), salivary glands (Murakami et al 2002a) and colon (Hase et al 2002). Cathelicidins have a wide spectrum of antimicrobial activity and have been shown to be active against Gram-negative and Grampositive bacteria (Travis et al 2000), fungi (Shin et al 2000) and enveloped viruses (Tamamura et al 1995).…”

Section: Introductionmentioning

confidence: 99%

Bioinformatic discovery and initial characterisation of nine novel antimicrobial peptide genes in the chicken

et al. 2004

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Antimicrobial peptides (AMPs) are essential components of innate immunity in a range of species fromDrosophila to humans and are generally thought to act by disrupting the membrane integrity of microbes. In order to discover novel AMPs in the chicken, we have implemented a bioinformatic approach that involves the clustering of more than 420,000 chicken expressed sequence tags (ESTs). Similarity searching of proteinspredicted to be encoded by these EST clusters-for homology to known AMPs has resulted in the in silico identification of full-length sequences for seven novel gallinacins (Gal-4 to Gal-10), a novel cathelicidin and a novel liver-expressed antimicrobial peptide 2 (LEAP-2) in the chicken. Differential gene expression of these novel genes has been demonstrated across a panel of chicken tissues. An evolutionary analysis of the gallinacin family has detected sites-primarily in the mature AMP-that are under positive selection in these molecules. The functional implications of these results are discussed.

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Cathelicidin Antimicrobial Peptides are Expressed in Salivary Glands and Saliva

Cited by 192 publications

References 33 publications

Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease

Antimicrobial Peptides in the Oral Environment: Expression and Function in Health and Disease

Antimicrobial protein hCAP18/LL‐37 is highly expressed in breast cancer and is a putative growth factor for epithelial cells

Bioinformatic discovery and initial characterisation of nine novel antimicrobial peptide genes in the chicken

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